Akinalytics
Polymer Blog
Technical Blog
John Garner, General ManagerA blog dedicated to answering technical questions in an open format relating to products from PolySciTech, a division of Akina, Inc.
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PLCL-PEG-PLCL from PolySciTech used in exploration of tumor cytokine interactions
Monday, August 19, 2024, 4:53 PM ET
Despite years of research, the biological and cellular mechanisms of cancer are not fully understood. Understanding the complex biological pathways and cascades involved in cancer growth and, notably, immunosuppression can unlock potential targets for cancer-specific therapies. Researchers at Johns Hopkins University, Stanford University, University of Ulsan, used PLCL-PEG-PLCL (AK109) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create a gel for delivery of METRNL cytokine as a means to explore the interaction of this cytokine with tumor cells. This research holds promise to improve immunotherapy approaches in the future. Read more: Jackson, Christopher M., Ayush Pant, Wikum Dinalankara, John Choi, Aanchal Jain, Ryan Nitta, Eli Yazigi et al. "The cytokine Meteorin-like inhibits anti-tumor CD8+ T cell responses by disrupting mitochondrial function." Immunity (2024). https://www.cell.com/immunity/abstract/S1074-7613(24)00352-2
“Tumor-infiltrating lymphocyte (TIL) hypofunction contributes to the progression of advanced cancers and is a frequent target of immunotherapy. Emerging evidence indicates that metabolic insufficiency drives T cell hypofunction during tonic stimulation, but the signals that initiate metabolic reprogramming in this context are largely unknown. Here, we found that Meteorin-like (METRNL), a metabolically active cytokine secreted by immune cells in the tumor microenvironment (TME), induced bioenergetic failure of CD8+ T cells. METRNL was secreted by CD8+ T cells during repeated stimulation and acted via both autocrine and paracrine signaling. Mechanistically, METRNL increased E2F-peroxisome proliferator-activated receptor delta (PPARd) activity, causingmitochondrial depolarization and decreased oxidative phosphorylation, which triggered a compensatory bioenergetic shift to glycolysis. Metrnl ablation or downregulation improved the metabolic fitness of CD8+ T cells and enhanced tumor control in several tumor models, demonstrating the translational potential of targeting the METRNL-E2F-PPARd pathway to support bioenergetic fitness of CD8+ TILs.”
PLCL-PEG-PLCL (Cat# AK109): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AK109#h
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PLCL from PolySciTech used in development of Neural Interface system
Monday, August 19, 2024, 4:47 PM ET
Developing the ability to interface between brain signals and digital equipment can be highly useful for patients suffering from paralysis or other disease states limiting their bodily mobility. Researchers at Seoul National University, Dankook University, University of Ulsan, Kwangwoon University, Korea University, Northwestern University, Gyeongsang National University, Sungkyunkwan University used PLCL (AP067) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create a biocompatible and flexible structure for minimally invasive implantation of a neural interface. This research holds promise to provide for improved prosthetics and other human-digital interfaces in the future. Read more: Bae, Jae-Young, Gyeong-Seok Hwang, Young-Seo Kim, Jooik Jeon, Minseong Chae, Joon-Woo Kim, Sian Lee et al. "A biodegradable and self-deployable electronic tent electrode for brain cortex interfacing." Nature Electronics (2024): 1-14. https://www.nature.com/articles/s41928-024-01216-x
“High-density, large-area electronic interfaces are a key component of brain–computer interface technologies. However, current designs typically require patients to undergo invasive procedures, which can lead to various complications. Here, we report a biodegradable and self-deployable tent electrode for brain cortex interfacing. The system can be integrated with multiplexing arrays and a wireless module for near-field communication and data transfer. It can be programmably packaged and self-deployed using a syringe for minimally invasive delivery through a small hole. Following delivery, it can expand to cover an area around 200 times its initial size. The electrode also naturally decomposes within the body after use, minimizing the impact of subsequent removal surgery. Through in vivo demonstrations, we show that our cortical-interfacing platform can be used to stimulate large populations of cortical activities.”
PLCL (Cat# AP067): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AP067#h
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PLGA-PEG-PLGA from PolySciTech used in evaluation of cytotoxicity test applicability
Thursday, August 15, 2024, 3:43 PM ET
In-vitro cytotoxicity tests are conducted as a surrogate for in-vivo testing to determine if a material has toxicity by monitoring its interactions with cells. Researchers at University of Nottingham utilized PLGA-PEG-PLGA (Cat# AK097) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to evaluate the interaction of this product with cells following the cytotoxicity tests. They found that the methodology applied for the test is important as the polymer exhibits acidic formation and other properties which yield false positives for cytotoxicity when no toxic effects are observed in animal model. This research holds promise to improve the methodology applied for evaluating toxicity of hydrogel materials. Read more: Stewart, Chloe L., Andrew L. Hook, Mischa Zelzer, Maria Marlow, and Anna M. Piccinini. "PLGA‐PEG‐PLGA hydrogels induce cytotoxicity in conventional in vitro assays." Cell Biochemistry and Function 42, no. 5 (2024): e4097. https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cbf.4097
“We identified that PLGA-PEG-PLGA hydrogels, which have been used in human clinical trials and possess a demonstrable safety profile, induced significant cytotoxicity in conventional in vitro assays. This major contradiction may lead to inconsistent and misleading toxicology due to the limited biological representation of these assays. Cytotoxicity evaluation is a crucial element of screening the biological response to new biomaterials. However, as standard test methods do not recapitulate the in vivo environment, tailored adaptations may be required to reflect the true biological response elicited toward novel biomaterials.”
PLGA-PEG-PLGA (Cat# AK097): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AK097#h
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Video: https://youtu.be/BB3q7G8FVeY
PLA from PolySciTech used in development of inulin-PLA copolymers for drug delivery
Tuesday, August 6, 2024, 4:00 PM ET
Inulin, a water-soluble polysaccharide from plants, can be used as a biomaterial for drug delivery and other applications. Researchers at University of Salerno, University of Naples Federico II, and Polish Academy of Sciences used two sizes of PLA (Cat # AP005, AP079) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to synthesize inulin-PLA. This research holds promise to provide for novel methods of drug delivery. Read more: Sardo, C., G. Auriemma, C. Mazzacano, C. Conte, V. Piccolo, T. Ciaglia, M. Denel-Bobrowska, A. B. Olejniczak, D. Fiore, and M. C. Proto. "Inulin Amphiphilic Copolymer-Based Drug Delivery: Unraveling the Structural Features of Graft Constructs.” Pharmaceutics 2024, 16, 971. https://www.mdpi.com/1999-4923/16/8/971
“In this study, the structural attributes of nanoparticles obtained by a renewable and nonimmunogenic “inulinated” analog of the “pegylated” PLA (PEG-PLA) were examined, together with the potential of these novel nanocarriers in delivering poorly water-soluble drugs. Characterization of INU-PLA assemblies, encompassing critical aggregation concentration (CAC), NMR, DLS, LDE, and SEManalyses, was conducted to elucidate the core/shell architecture of the carriers and in vitro cytoand hemo-compatibility were assayed. The entrapment and in vitro delivery of sorafenib tosylate (ST) were also studied. INU-PLA copolymers exhibit distinctive features: (1) Crew-cut aggregates are formed with coronas of 2–4 nm; (2) a threshold surface density of 1 INU/nm2 triggers a configuration change; (3) INU surface density influences PLA core dynamics, with hydrophilic segment stretching affecting PLA distribution towards the interface. INU-PLA2 NPs demonstrated an outstanding loading of ST and excellent biological profile, with effective internalization and ST delivery to HepG2 cells, yielding a comparable IC50.”
PLA (Cat# AP005): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AP005#h
PLA (Cat# AP079): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AP079#h
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PEG-PLGA from PolySciTech used in development of triple-chemotherapy loaded nanoparticles
Tuesday, August 6, 2024, 3:59 PM ET
Cancer is a complex disease often requiring multiple drugs to elicit effective treatment. Researchers at University of Ottawa and University of Toronto used mPEG-PLGA (Cat# AK148) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles loaded with cisplatin, olaparib, and metformin for cancer therapy. This research holds promise to improve treatment of cancer. Read more: Durocher, Emma, Sean McGrath, Esha Gahunia, Naomi Matsuura, and Suresh Gadde. "Development of 3-in-1 nanotherapeutic strategies for ovarian cancer." bioRxiv (2024): 2024-07. https://www.biorxiv.org/content/10.1101/2024.07.17.604002.abstract
“Among gynecological cancers, ovarian cancer causes the most fatality. Platin-based chemotherapy is the primary therapeutic option, but it is limited by a variety of drug resistance mechanisms. Ovarian cancer is a complex and challenging disease to treat, and combination approaches have shown stronger efficacy than a single drug alone. However, they still need to overcome challenges, such as the non-selective distribution of drugs, and side effects caused by each drug in the combination. To overcome these issues, here we explored a 3-in-1 combination nanotherapeutic approach containing cisplatin, olaparib, and metformin for ovarian cancer. To encapsulate hydrophilic cisplatin and metformin inside the nanoparticle (NP) core, we developed cisplatin polymer prodrugs and metformin derivatives. Our results showed successful development of 3-in-1 NPs containing cisplatin, olaparib, and metformin, and they are stable in the physiological conditions. In vitro evaluation showed each agent in the 3-in-1 NPs is active and exerts therapeutic effects, contributing to ovarian cancer cell killing at lower concentrations. These results provide insight into developing novel nanotherapeutic strategies for improving ovarian cancer treatment.”
mPEG-PLGA (Cat# AK148): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AK148#h
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Video: https://youtu.be/WcgTeg291Kw
PLGA-PEG-Mal and PLGA-FKR648 from PolySciTech used in development of Mucin-16 cancer targeted nanoparticles
Tuesday, July 23, 2024, 8:32 AM ET
Targeting to cancer relies on differences between healthy cells and cancerous ones. For example, differences in mucin 16 can be used as a target moiety for drug delivery. Researchers at University of Portugal used PLGA-PEG-Mal (Cat# AI110) and PLGA-FKR648 (Cat# AV015) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles with mucin-based targeting for cancer therapy. This research holds promise to improve cancer treatments in the future. Read more: Freitas, Rui, Eduardo Ferreira, Andreia Miranda, Dylan Ferreira, Marta Relvas-Santos, Flávia Castro, Beatriz Santos et al. "Targeted and Self-Adjuvated Nanoglycovaccine Candidate for Cancer Immunotherapy." ACS nano 18, no. 14 (2024): 10088-10103. https://pubs.acs.org/doi/abs/10.1021/acsnano.3c12487
“Advanced-stage solid primary tumors and metastases often express mucin 16 (MUC16), carrying immature glycans such as the Tn antigen, resulting in specific glycoproteoforms not found in healthy human tissues. This presents a valuable approach for designing targeted therapeutics, including cancer glycovaccines, which could potentially promote antigen recognition and foster the immune response to control disease spread and prevent relapse. In this study, we describe an adjuvant-free poly(lactic-co-glycolic acid) (PLGA)-based nanoglycoantigen delivery approach that outperforms conventional methods by eliminating the need for protein carriers while exhibiting targeted and adjuvant properties. To achieve this, we synthesized a library of MUC16-Tn glycoepitopes through single-pot enzymatic glycosylation, which were then stably engrafted onto the surface of PLGA nanoparticles, generating multivalent constructs that better represent cancer molecular heterogeneity. These glycoconstructs demonstrated affinity for Macrophage Galactose-type Lectin (MGL) receptor, known to be highly expressed by immature antigen-presenting cells, enabling precise targeting of immune cells. Moreover, the glycopeptide-grafted nanovaccine candidate displayed minimal cytotoxicity and induced the activation of dendritic cells in vitro, even in the absence of an adjuvant. In vivo, the formulated nanovaccine candidate was also nontoxic and elicited the production of IgG specifically targeting MUC16 and MUC16-Tn glycoproteoforms in cancer cells and tumors, offering potential for precise cancer targeting, including targeted immunotherapies. KEYWORDS: glycovaccines nanovaccines cancer immunotherapy cancer glycosylation glycoantigens glycoconjugates”
PLGA-PEG-Mal (Cat# AI110): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AI110#h
PLGA-FKR648 (Cat# AV015): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AV015#h
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PEG-PLGA and PLGA-NHS from PolySciTech used in development of cancer targeting nanoparticles
Tuesday, July 23, 2024, 8:31 AM ET
Prostate cancer accounts for 14.9% of all new cancer cases. Researchers from Howard University used PEG-PLGA (Cat# AK029) and PLGA-NHS (Cat# AI097) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles with PSMA targeting to prostate cancer cells. This research holds promise to provide for treatment of cancer. Read more: Adekiya, Tayo Alex, Tamaro Hudson, Oladapo Bakare, Edmund E. Ameyaw, Amusa Adebayo, Oluwabukunmi Olajubutu, and Simeon K. Adesina. "PSMA-targeted combination brusatol and docetaxel nanotherapeutics for the treatment of prostate cancer." Biomedicine & Pharmacotherapy 177 (2024): 117125. https://www.sciencedirect.com/science/article/pii/S0753332224010096
“Highlights: PSMA-targeting facilitates prostate cancer-specific drug delivery. 10 % nanoparticle surface density of PSMA targeting ligand is optimal for uptake. PSMA-targeted drug-loaded particles show cytotoxicity to the cell lines tested. PSMA-targeted nanoparticles suppress tumor growth in xenograft models. Brusatol-containing nanoparticle formulations aid reduction in tumor volume. Abstract: Active targeting to cancer involves exploiting specific interactions between receptors on the surface of cancer cells and targeting moieties conjugated to the surface of vectors such that site-specific delivery is achieved. Prostate specific membrane antigen (PSMA) has proved to be an excellent target for active targeting to prostate cancer. We report the synthesis and use of a PSMA-specific ligand (Glu-NH-CO-NH-Lys) for the site-specific delivery of brusatol- and docetaxel-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles to prostate cancer. The PSMA targeting ligand covalently linked to PLGA-PEG3400 was blended with methoxyPEG-PLGA to prepare brusatol- and docetaxel-loaded nanoparticles with different surface densities of the targeting ligand. Flow cytometry was used to evaluate the impact of different surface densities of the PSMA targeting ligand in LNCaP prostate cancer cells at 15 min and 2 h. Cytotoxicity evaluations of the targeted nanoparticles reveal differences based on PSMA expression in PC-3 and LNCaP cells. In addition, levels of reactive oxygen species (ROS) were measured using the fluorescent indicator, H2DCFDA, by flow cytometry. PSMA-targeted nanoparticles loaded with docetaxel and brusatol showed increased ROS generation in LNCaP cells compared to PC-3 at different time points. Furthermore, the targeted nanoparticles were evaluated in male athymic BALB/c mice implanted with PSMA-producing LNCaP cell tumors. Evaluation of the percent relative tumor volume show that brusatol-containing nanoparticles show great promise in inhibiting tumor growth. Our data also suggest that the dual drug-loaded targeted nanoparticle platform improves the efficacy of docetaxel in male athymic BALB/c mice implanted with PSMA-producing LNCaP cell tumors.”
PEG-PLGA (Cat# AK029): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AK029#h
PLGA-NHS (Cat# AI097): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AI097#h
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PLGA from PolySciTech used in development of ultrasound triggered delivery of genes for bone cancer treatment
Tuesday, July 23, 2024, 8:30 AM ET
Bone cancer is particularly difficult to treat due to
its poor response to conventional chemotherapy and other, non-surgical,
methods. Researchers at Chongqing Medical University used PLGA (cat# AP041)
from PolySciTech Division of Akina, Inc. (www.polyscitech.com)
to create nanobubbles for transfer of genes into target cells using ultrasound.
This research holds promise to provide for non-invasive therapies for bone
cancer. Read more: Ren, Honglei, Shanlin Xiang, Aiguo Liu, Qian Wang, Nian
Zhou, and Zhenming Hu. "A noval noninvasive targeted therapy for
osteosarcoma: the combination of LIFU and ultrasound-magnetic-mediated
SPIO/TP53/PLGA nanobubble." Frontiers in Bioengineering and Biotechnology
12 (2024): 1418903. https://www.frontiersin.org/articles/10.3389/fbioe.2024.1418903/full
“Purpose: Osteosarcoma (OS) is the most common type of
primary malignant bone tumor. Transducing a functional TP53 gene can
effectively inhibit OS cell activity. Poly lactic acid-glycolic acid (PLGA)
nanobubbles (NBs) mediated by focused ultrasound (US) can introduce exogenous
genes into target cells in animal models, but this technique relies on the
passive free diffusion of agents across the body. The inclusion of
superparamagnetic iron oxide (SPIO) in microbubbles allows for magnetic-based
tissue localization. A low-intensity-focused ultrasound (LIFU) instrument was
developed at our institute, and different intensities of LIFU can either
disrupt the NBs (RLI-LIFU) or exert cytocidal effects on the target tissues
(RHI-LIFU). Based on these data, we performed US-magnetic-mediated TP53-NB
destruction and investigated its ability to inhibit OS growth when combined
with LIFU both in vitro and in vivo. Methods: Several SPIO/TP53/PLGA (STP) NB
variants were prepared and characterized. For the in vitro experiments, HOS and
MG63 cells were randomly assigned into five treatment groups. Cell
proliferation and the expression of TP53 were detected by CCK8, qRT-PCR and
Western blotting, respectively. In vivo, tumor-bearing nude mice were randomly
assigned into seven treatment groups. The iron distribution of Perls’ Prussian
blue-stained tissue sections was determined by optical microscopy. TUNEL-DAPI
was performed to examine apoptosis. TP53 expression was detected by qRT-PCR and
immunohistochemistry. Results: SPIO/TP53/PLGA NBs with a particle size of approximately
200 nm were prepared successfully. For in vitro experiments,
ultrasound-targeted transfection of TP53 overexpression in OS cells and
efficient inhibition of OS proliferation have been demonstrated. Furthermore,
in a tumor-bearing nude mouse model, RLI-LIFU-magnetic-mediated SPIO/TP53/PLGA
NBs increased the transfection efficiency of the TP53 plasmid, resulting in
apoptosis. Adding RHI-LIFU to the treatment regimen significantly increased the
apoptosis of OS cells in vivo. Conclusion: Combining LIFU and
US-magnetic-mediated SPIO/TP53/PLGA NB destruction is potentially a novel
noninvasive and targeted therapy for OS.”
PEG-PLA AP041: https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AP041#h
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PEG-PLGA from PolySciTech used in development of oral delivery system for Enfuvirtide as HIV treatment
Friday, July 19, 2024, 4:39 PM ET
Many antiviral agents have poor uptake across the intestine which limits them to only being administered by parental routes. For patient convenience, comfort, and compliance delivery by oral route is preferable. Researchers at The University of Queensland used PEG-PLGA (cat# AK026) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create oral nanoparticles for delivery of Enfuvirtide as an antiviral agent. This research holds promise to provide additional treatment for HIV/AIDS. Read more: Pang, Huiwen, Zhi Qu, Vinod Kumar, Yinuo Wang, Youzhi Wu, Min‐Hsuan Lin, David Harrich, and Felicity Y. Han. "Novel Delivery Systems for Oral Administration of Enfuvirtide: New Treatment Options for HIV/AIDS." Advanced Therapeutics (2024): 2300439. https://onlinelibrary.wiley.com/doi/abs/10.1002/adtp.202300439
“Enfuvirtide (T-20) is a synthetic peptide fusion inhibitor for the human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS). However, the peptide nature limits a wider application of T-20 with subcutaneous injection (Fuzeon) the only available formulation. In this groundbreaking study, it is sought to overcome this limitation by employing poly lactic-co-glycolic acid (PLGA) and alginate to create novel oral delivery systems for T-20. Remarkably, this investigation marks the first instance of assessing the efficacy of oral delivery systems in mice. Notably, both the PLGA and alginate formulations exhibit the capability to sustain T-20 release, maintaining detectable levels in the bloodstream of mice for over 24 h after a single dose. By venturing into the realm of oral T-20 delivery, this study opens avenues for the prospective development of oral formulations of T-20, potentially leading to their evaluation in clinical trials.”
PEG-PLA AK026: https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AK026#h
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PEG-PLA from PolySciTech used in development of intracranial delivery of drugs for brain treatment
Friday, July 19, 2024, 4:09 PM ET
Delivery of medicinal molecules into brain tissue is complicated by the blood-brain-barrier which prevents many drugs from crossing into the brain tissue. Researchers at University of Utah used PEG-PLA (cat# AK009) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nano emulsions which could be triggered through the cranium using ultrasound technology. This research holds promise to provide treatment for a variety of neurological conditions. Read more: Wilson, Matthew G., Thomas S. Riis, and Jan Kubanek. "Controlled ultrasonic interventions through the human skull." Frontiers in Human Neuroscience 18 (2024): 1412921. https://www.frontiersin.org/articles/10.3389/fnhum.2024.1412921/full
“Transcranial focused ultrasound enables precise and non-invasive manipulations of deep brain circuits in humans, promising to provide safe and effective treatments of various neurological and mental health conditions. Ultrasound focused to deep brain targets can be used to modulate neural activity directly or localize the release of psychoactive drugs. However, these applications have been impeded by a key barrier—the human skull, which attenuates ultrasound strongly and unpredictably. To address this issue, we have developed an ultrasound-based approach that directly measures and compensates for the ultrasound attenuation by the skull. No additional skull imaging, simulations, assumptions, or free parameters are necessary; the method measures the attenuation directly by emitting a pulse of ultrasound from an array on one side of the head and measuring with an array on the opposite side. Here, we apply this emerging method to two primary future uses—neuromodulation and local drug release. Specifically, we show that the correction enables effective stimulation of peripheral nerves and effective release of propofol from nanoparticle carriers through an ex vivo human skull. Neither application was effective without the correction. Moreover, the effects show the expected dose-response relationship and targeting specificity. This article highlights the need for precise control of ultrasound intensity within the skull and provides a direct and practical approach for addressing this lingering barrier.”
PEG-PLA AK009: https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AK009#h
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PLA-PEG-PLA thermogel from PolySciTech used in development of celecoxib delivery system for treatment of breast cancer
Monday, July 8, 2024, 4:27 PM ET
Breast cancer accounts for 30% of all new cancers in women. There are 670,000 deaths per year due to this disease. Researchers at University of Oklahoma, Medical College of Wisconsin, and Thomas Jefferson University used PLA-PEG-PLA (cat# AK100) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop a thermally responsive hydrogel as a carrier of nanoparticles for delivery of celecoxib. This research holds promise to provide for improved treatment of breast cancer. Read more: Simmons, Reese, Hiroyasu Kameyama, Seiko Kubota, Yunguang Sun, John F. Langenheim, Rana Ajeeb, Tristan S. Shao et al. "Sustained delivery of celecoxib from nanoparticles embedded in hydrogel injected into the biopsy cavity to prevent biopsy-induced breast cancer metastasis." Breast Cancer Research and Treatment (2024): 1-13. https://link.springer.com/article/10.1007/s10549-024-07410-x
“Purpose: We have previously reported that protracted Cyclooxygenase-2 (COX-2) activity in bone marrow-derived cells (BMDCs) infiltrating into biopsy wounds adjacent to the biopsy cavity of breast tumors in mice promotes M2-shift of macrophages and pro-metastatic changes in cancer cells, effects which were suppressed by oral administration of COX-2 inhibitors. Thus, local control of COX-2 activity in the biopsy wound may mitigate biopsy-induced pro-metastatic changes. Methods: A combinatorial delivery system—thermosensitive biodegradable poly(lactic acid) hydrogel (PLA-gel) incorporating celecoxib-encapsulated poly(lactic-co-glycolic acid) nanoparticles (Cx-NP/PLA-gel)—was injected into the biopsy cavity of Py230 murine breast tumors to achieve local control of COX-2 activity in the wound stroma. Results: A single intra-biopsy cavity injection of PLA-gel loaded with rhodamine-encapsulated nanoparticles (NPs) showed sustained local delivery of rhodamine preferentially to infiltrating BMDCs with minimal to no rhodamine uptake by the reticuloendothelial organs in mice. Moreover, significant reductions in M2-like macrophage density, cancer cell epithelial-to-mesenchymal transition, and blood vessel density were observed in response to a single intra-biopsy cavity injection of Cx-NP/PLA-gel compared to PLA-gel loaded with NPs containing no payload. Accordingly, intra-biopsy cavity injection of Cx-NP/PLA-gel led to significantly fewer metastatic cells in the lungs than control-treated mice. Conclusion: This study provides evidence for the feasibility of sustained, local delivery of payload preferential to BMDCs in the wound stroma adjacent to the biopsy cavity using a combinatorial delivery system to reduce localized inflammation and effectively mitigate breast cancer cell dissemination. Keywords: Hydrogel, Nanoparticle, Metastasis, Biopsy, Biopsy site marker, Local drug delivery”
PLA-PEG-PLA AK100: https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AK100#h
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mPEG-PLGA from PolySciTech used in development of RNA delivery system for control of gene expression
Monday, July 1, 2024, 2:40 PM ET
As a general rule, DNA is transcribed into single-stranded RNA which is then used to manufacture proteins. The original DNA of a cell is generally set and can not be easily edited however RNA is a dynamic process in which the single-stranded ‘message-carrier’ is constantly created, used, and destroyed. By applying messenger RNA (mRNA for transcription) of a wanted protein and silencing RNA (siRNA which selectively binds to specific coding of mRNA to prevent it from being converted to a protein) it is possible to control the expression of genes at a cellular level for a fixed period of time. Researchers at University of Ottawa used mPEG-PLGA (AK026) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles for the simultaneous delivery of mRNA and siRNA to control gene/protein expression. This research holds promise to provide for treatment of a wide range of diseases. Read more: Manturthi, Shireesha, Sara El-Sahli, Yuxia Bo, Emma Durocher, Melanie Kirkby, Alyanna Popatia, Karan Mediratta et al. "Nanoparticles co-delivering siRNA and mRNA for simultaneous restoration and silencing of gene/protein expression in vitro and in vivo." bioRxiv (2024): 2024-06. https://www.biorxiv.org/content/10.1101/2024.06.22.600196.abstract
“RNA-based agents such as siRNA, miRNA, and mRNA can selectively manipulate gene expression/proteins and have the potential to revolutionize the current therapeutic strategies for various diseases, including cancer. To address the poor stability and inherent limitations of RNA agents, nanoparticle (NP) platforms have been developed to deliver functional mRNA or siRNA inside the cells. Recent studies have focused on either siRNA to knock down proteins causing drug resistance or mRNA technology to introduce tumor suppressors. However, complex diseases like cancer need multi-targeted approaches to selectively target multiple gene expressions/proteins. In this proof-of-concept study, we developed co-delivery nanoparticles containing Luc-mRNA and siRNA-GFP as model RNA agents ((M+S)-NPs) and assessed their effects in vitro and in vivo. Our studies show that NPs can effectively deliver both functional mRNA and siRNA together, simultaneously impacting the expression of two genes/proteins in vitro. Additionally, after in vivo administration, co-delivery NPs successfully knocked down GFP while introducing luciferase in a TNBC mouse model, indicating our NPs have the potential to develop RNA-based anticancer therapeutics. These studies pave the way to develop RNA-based, multitargeted, multi-delivery approaches for complex diseases like cancer. Keywords: nanoparticles, siRNA, mRNA, co-delivery, gene, protein, restoration and knockdown.”
mPEG-PLGA AK026: https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AK026#h
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PLGA-PEG-PLGA from PolySciTech used in development of ocular release platform for treatment of secondary cataracts
Thursday, June 27, 2024, 11:47 AM ET
Cataracts are the second leading cause of blindness with over 100 million cataract surgeries performed worldwide. A common complication from cataract surgery is the formation of ‘secondary cataracts’ created by tissue response to the surgical process. Researchers at Rowan University, Philadelphia College of Osteopathic Medicine, Genisphere, LLC, and OcuMedic, Inc., used thermogelling PLGA-PEG-PLGA (cat# AK097) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create a gel formulation for the controlled release of therapeutic DNA which reduces secondary cataract formation. This research holds promise to provide for treatment against cataract-induced blindness. Read more: Vardar, Camila, Mindy George-Weinstein, Robert Getts, and Mark E. Byrne. "Evaluation of Dose–Response Relationship in Novel Extended Release of Targeted Nucleic Acid Nanocarriers to Treat Secondary Cataracts." Journal of Ocular Pharmacology and Therapeutics (2024). https://www.liebertpub.com/doi/abs/10.1089/jop.2024.0024
“Abstract: Purpose: The present study aimed to determine the dose–response relationship between targeted nanocarriers released from a novel, sustained release formulation and their ability to specifically deplete cells responsible for the development of posterior capsular opacification (PCO) in month-long, dynamic cell cultures. Methods: Injectable, thermosensitive poly(D,L-lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic-co-glycolic acid) triblock copolymer hydrogels were loaded with either a low or a high dose of doxorubicin-loaded antibody-targeted nanocarriers (G8:3DNA:Dox). Human rhabdomyosarcoma cells, selected for their expression of PCO marker brain-specific angiogenesis inhibitor 1 (BAI1), were kept under dynamic media flow and received either a low or high dose of nanocarriers. Cells were fixed and stained at predetermined time points to evaluate targeted depletion of BAI1+ cells. Results: A lower dose of nanocarriers in hydrogel depleted BAI1+ cells at a slower rate than the higher dose, whereas both reached over 90% BAI1+ cellular nonviability at 28 days. Both treatment groups also significantly lowered the relative abundance of BAI1+ cells in the population compared with the control group. Conclusions: Controlled release of a lower dose of nanocarriers can still achieve therapeutically relevant effects in the prevention of PCO, while avoiding potential secondary effects associated with the administration of a higher dose.”
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PLGA from PolySciTech used in development of anti-viral delivery system for treatment of respiratory diseases
Wednesday, June 26, 2024, 4:47 PM ET
The pandemic highlighted the need to provide for reliable treatment of respiratory diseases. One way to treat a viral respiratory disease is to deliver a high dose of antiviral agent in a localized manner to the respiratory tissue. This is optimally achieved with an inhaled formulation which can deliver drugs to the affect lung and throat tissues quickly. Researchers at University of Texas at Arlington and University of Southern Mississippi used PLGA (catalog # AP040) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop a nanoparticle drug delivery system for inhaled delivery of antiviral Remdesivir. This antiviral agent can be used as a therapeutic option for respiratory diseases in the future. Read more: Chintapula, Uday, Shazeed-Ul Karim, Priyanka Raghunathan Iyer, Haritha Asokan-Sheeja, Biswas Neupane, Farzana Nazneen, He Dong, Fengwei Bai, and Kytai T. Nguyen. "A novel nanocomposite drug delivery system for SARS-CoV-2 infections." (2024). https://www.researchgate.net/profile/Farzana-Nazneen-2/publication/381502779_A_novel_nanocomposite_drug_delivery_system_for_SARS-CoV-2_infections/links/6671dd25b769e7691940c595/A-novel-nanocomposite-drug-delivery-system-for-SARS-CoV-2-infections.pdf
“To develop an inhalable drug delivery system, we synthesized poly (lactic-co-glycolic acid) nanoparticles with Remdesivir (RDV NPs) as an antiviral agent against SARS-CoV-2 replication and formulated Remdesivir-loaded nanocomposites (RDV NCs) via coating of RDV NPs with novel supramolecular cellpenetrating peptide nanofibers (NFs) to enhance cellular uptake and intracellular drug delivery. RDV NPs and RDV NCs were characterized using variou techniques, including Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), and fluorescent microscopy. The cytotoxicity of RDV NCs was assessed in Vero E6 cells and primary human lung epithelial cells, with no significant cytotoxicity observed up to 1000 mgmL−1 and 48 h. RDV NCs were spherically shaped with a size range of 200300 nm and a zeta potential of ∼+31 mV as well as indicating the presence of coated nanofibers. Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR), immunofluorescence and plaque assays of SARS-CoV-2 infected Vero E6 treated with RDV NCs showed significantly higher antiviral activities compared to those of free drug and uncoated RDV NPs. RDV NCs exhibited high antiviral activity against SARS-CoV-2, and the nanocomposite platform has the potential to be developed into an inhalable drug delivery system for other viral infections in the lungs.”
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PLGA-PEG-NH2 from PolySciTech used in development of cerebrospinal-protein corona-covered nanoparticles to study neural cell interactions
Wednesday, June 19, 2024, 9:33 AM ET
Treatment of diseases within the brain, ranging from glioblastoma to Alzheimer's, remains difficult in part due to the blood-brain-barrier. The details of the interactions between proteins and neural cells remain poorly understood which inhibits development of therapies to deliver medicinal molecules into the brain. Researchers at the University of Technology Sydney, The University of Melbourne, and The University of Adelaide used PLGA-PEG-NH2 (cat# AI169) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles covered with cerebrospinal proteins. They used these to research the interactions of such particles with neural cells. This research holds promise to improve drug delivery to brain tissue for treatment of a variety of disease states. Read more: Morshed, Nabila, Claire Rennie, Matthew Faria, Lyndsey E. Collins-Praino, and Andrew Care. "Protein Coronas Derived from Cerebrospinal Fluid Enhance the Interactions Between Nanoparticles and Brain Cells." bioRxiv (2024): 2024-05. https://www.biorxiv.org/content/10.1101/2024.05.31.596763.abstract
“Neuronanomedicine harnesses nanoparticle technology for the treatment of neurological disorders. An unavoidable consequence of nanoparticle delivery to biological systems is the formation of a protein corona on the nanoparticle surface. Despite the well-established influence of the protein corona on nanoparticle behavior and fate, as well as FDA approval of neuro-targeted nanotherapeutics, the effect of a physiologically relevant protein corona on nanoparticle-brain cell interactions is insufficiently explored. Indeed, less than 1% of protein corona studies have investigated protein coronas formed in cerebrospinal fluid (CSF), the fluid surrounding the brain. Herein, we utilize two clinically relevant polymeric nanoparticles (PLGA and PLGA-PEG) to evaluate the formation of serum and CSF protein coronas. LC-MS analysis revealed distinct protein compositions, with selective enrichment/depletion profiles. Following incubation with brain cells, serum and CSF coronas on PLGA particles showed enhanced associations with all cell types as compared to their corresponding corona on PLGA-PEG particles. CSFderived protein coronas on PLGA nanoparticles, specifically, showed the greatest nanoparticle-cell interactions, with Pearson’s correlation analysis revealing that proteins associated with enhanced nanoparticle-cell interactions were exclusively enriched in this protein corona. This study demonstrates the importance of correct choice of physiologically relevant biological fluids, and its influence on the formation of the protein corona, subsequent nanoparticle-cell interactions. Keywords: protein corona; bio-nano interactions, neuronanomedicine; cerebrospinal fluid; neurons; glia; targeted drug delivery”
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mPEG-PLGA from PolySciTech used in development of polymeric nanoparticles combination therapy.
Friday, June 14, 2024, 5:01 PM ET
Cancer typically requires multiple drug therapies for its treatment however delivery of medicinal molecules is difficult. Researchers at University of Adelaide utilized mPEG-PLGAs (Cat# AK010 and AK026) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop multi-drug delivery nanoparticles for cancer therapy applications. This research holds promise to provide for improved therapy against cancer in the future. Read more: Jin, Song, Zhenwei Lan, Guangze Yang, Xinyu Li, Javen Qinfeng Shi, Yun Liu, and Chun‐Xia Zhao. "Computationally guided design and synthesis of dual‐drug loaded polymeric nanoparticles for combination therapy." Aggregate (2024): e606. https://onlinelibrary.wiley.com/doi/abs/10.1002/agt2.606
“Single-drug therapies or monotherapies are often inadequate, particularly in the case of life-threatening diseases like cancer. Consequently, combination therapies emerge as an attractive strategy. Cancer nanomedicines have many benefits in addressing the challenges faced by small molecule therapeutic drugs, such as low water solubility and bioavailability, high toxicity, etc. However, it remains a significant challenge in encapsulating two drugs in a nanoparticle. To address this issue, computational methodologies are employed to guide the rational design and synthesis of dual-drug-loaded polymer nanoparticles while achieving precise control over drug loading. Based on the sequential nanoprecipitation technology, five factors are identified that affect the formulation of drug candidates into dual-drug loaded nanoparticles, and then screened 176 formulations under different experimental conditions. Based on these experimental data, machine learning methods are applied to pin down the key factors. The implementation of this methodology holds the potential to significantly mitigate the complexities associated with the synthesis of dual-drug loaded nanoparticles, and the co-assembly of these compounds into nanoparticulate systems demonstrates a promising avenue for combination therapy. This approach provides a new strategy for enabling the streamlined, high-throughput screening and synthesis of new nanoscale drug-loaded entities.”
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PLGA-Rhodamine used in development of micropatches for immunotherapy of cancer.
Thursday, May 30, 2024, 3:40 PM ET
B-Cells are macrophages which play a key role in the immune response. These cells can be leveraged to modify the adaptive immune response. Researchers at Harvard University, used PLGA-Rhodamine (Cat# AV011) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) as part of developing patches to target B-cells and induce them to raise an immune response against cancer. This research holds promise to provide for therapy against cancer. Read more: Prakash, Supriya, Ninad Kumbhojkar, Alexander P. Gottlieb, Kyung-Soo Park, Neha Kapate, and Samir Mitragotri. "Polymer Micropatches as B-Cell Engagers." ACS Applied Materials & Interfaces (2024). https://pubs.acs.org/doi/abs/10.1021/acsami.4c04385
“ABSTRACT: B cells, despite their several unique functionalities, remain largely untapped for use as an adoptive cell therapy and are limited to in vitro use for antibody production. B cells can be easily sourced, they possess excellent lymphoid-homing capabilities, and they can act as antigen-presenting cells (APCs), offering an alternative to dendritic cells (DCs), which have shown limited efficacy in the clinical setting. Soluble factors such as IL-4 and anti-CD40 antibody can enhance the activation, survival, and antigen-presenting capabilities of B cells; however, it is difficult to attain sufficiently high concentrations of these biologics to stimulate B cells in vivo. Micropatches as Cell Engagers (MACE) are polymeric microparticles, surface functionalized with anti-CD40 and anti-IgM, which can attach to B cells and simultaneously engage multiple B-cell receptors (BCR) and CD40 receptors. Stimulation of these receptors through MACE, unlike free antibodies, enhanced the display of costimulatory molecules on the B-cell surface, increased B-cell viability, and improved antigen presentation by B cells to T cells in vitro. B-cell activation by MACE further synergized with soluble IL-4 and anti-CD40. MACE also elicited T-cell chemokine secretion by B cells. Upon intravenous adoptive transfer, MACE-bound B cells homed to the spleen and lymph nodes, key sites for antigen presentation to T cells. Adoptive transfer of MACE-B cells pulsed with the CD4+ and CD8+ epitopes of ovalbumin significantly delayed tumor progression in a murine subcutaneous EG7-OVA tumor model, demonstrating the functional benefit conferred to B cells by MACE. KEYWORDS: B cells, B-cell activation, MACE, APC, cellular vaccine, cancer vaccine”
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Fluorescent Polylactide from PolySciTech used in development of bioadhesive particles for vaginal infection prevention
Friday, May 17, 2024, 8:23 AM ET
Many sexually transmitted diseases as well as other infections enter by the vaginal route. Providing for a long-acting infection prevention system can reduce exposure and lower the risk of disease. Researchers at Yale University and University of Alabama at Birmingham used PLA-FITC (Cat# AV039) from from PolySciTech Division of Akina, Inc. (www.polyscitech.com) as part of their work in developing mucoadhesive nanoparticles for vaginal protection. This research holds promise to provide for protection from infection. Read more: Grun, Molly K., Praveen Honhar, Yazhe Wang, Samantha Rossano, Minsoo Khang, Hee Won Suh, Krista Fowles et al. "Pilot PET study of vaginally administered bioadhesive nanoparticles in cynomolgus monkeys: Kinetics and safety evaluation." Bioengineering & Translational Medicine (2024): e10661. https://aiche.onlinelibrary.wiley.com/doi/abs/10.1002/btm2.10661
“Long-lasting vaginal dosage forms could improve the therapeutic efficacy of vaginal microbicides, but achieving long-term delivery to the vaginal canal has been a significant challenge. To advance understanding of vaginal dosage retention and biodistribution, we describe a method of noninvasive imaging with 89Zr-labeled bioadhesive nanoparticles (BNPs) in non-human primates. We additionally examined the safety of repeated BNP application. BNPs administered vaginally to cynomolgus monkeys were still detected after 24 h (1.7% retention) and 120 h (0.1% retention). BNPs did not translocate to the uterus or into systemic circulation. Analysis of inflammatory biomarkers in the vaginal fluid and plasma suggest that BNPs are safe and biocompatible, even after multiple doses. BNPs are a promising delivery vehicle for vaginally administered therapeutics. Further studies using the non-human primate imaging materials and methods developed here could help advance clinical translation of BNPs and other long-lasting vaginal dosage forms.”
AV039 (https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AV039#h)
PLGA-Amine from PolySciTech used in development of nanoparticle targeting system for heart therapy.
Friday, May 10, 2024, 4:52 PM ET
Delivery of medicinal molecules to the heart is challenging as many nanoparticles are taken up by either liver or kidney clearance. Researchers at Case Western Reserve University and Bioheights LLC use PLGA-NH2 (catalog AI062) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) in development of fluorescently stained polymer carriers to improve delivery of nanoparticles to cardiovascular tissues. This research holds promise to provide for targeted drug delivery to the heart for treatment of cardiovascular diseases. Read more: Switala, Lauren, Lin Di, Huiyun Gao, Courteney Asase, Matthew Klos, Palanivel Rengasamy, Daria Fedyukina, and Andrei Maiseyeu. "Engineered nanoparticles promote cardiac tropism of AAV vectors." Journal of Nanobiotechnology 22, no. 1 (2024): 223. https://link.springer.com/article/10.1186/s12951-024-02485-6
“Cardiac muscle targeting is a notoriously difficult task. Although various nanoparticle (NP) and adeno-associated viral (AAV) strategies with heart tissue tropism have been developed, their performance remains suboptimal. Significant off-target accumulation of i.v.-delivered pharmacotherapies has thwarted development of disease-modifying cardiac treatments, such as gene transfer and gene editing, that may address both rare and highly prevalent cardiomyopathies and their complications. Here, we present an intriguing discovery: cargo-less, safe poly (lactic-co-glycolic acid) particles that drastically improve heart delivery of AAVs and NPs. Our lead formulation is referred to as ePL (enhancer polymer). We show that ePL increases selectivity of AAVs and virus-like NPs (VLNPs) to the heart and de-targets them from the liver. Serotypes known to have high (AAVrh.74) and low (AAV1) heart tissue tropisms were tested with and without ePL. We demonstrate up to an order of magnitude increase in heart-to-liver accumulation ratios in ePL-injected mice. We also show that ePL exhibits AAV/NP-independent mechanisms of action, increasing glucose uptake in the heart, increasing cardiac protein glycosylation, reducing AAV neutralizing antibodies, and delaying blood clearance of AAV/NPs. Current approaches utilizing AAVs or NPs are fraught with challenges related to the low transduction of cardiomyocytes and life-threatening immune responses; our study introduces an exciting possibility to direct these modalities to the heart at reduced i.v. doses and, thus, has an unprecedented impact on drug delivery and gene therapy. Based on our current data, the ePL system is potentially compatible with any therapeutic modality, opening a possibility of cardiac targeting with numerous pharmacological approaches.”
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Fluorescently labelled PLGA from PolySciTech used in development of cell-modulating system for cancer immunotherapy
Wednesday, April 24, 2024, 2:56 PM ET
Delivery of drugs into solid tumors as well as cancers immunosuppressive effect on the surrounding microenvironment makes treatment of cancer challenging. One strategy to overcome this is to utilize a surface-attaching structure which promotes immune cells in the region of cancer to become pro-inflammatory and anti-tumor thus leading the human immune system to fight the cancer. Researchers at Harvard University used PLGA-rhodamine (AV011) and PLGA-Cyanine5 (AV034) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop ‘backpacks’ small structures which attach to myeloid cells and encourages them to participate in immune attack of cancer. This research holds promise to treat many forms of aggressive cancer including immunosuppressive tumors. Read more: Kapate, Neha, Michael Dunne, Alexander P. Gottlieb, Malini Mukherji, Vineeth Chandran Suja, Supriya Prakash, Kyung Soo Park, Ninad Kumbhojkar, Jennifer L. Guerriero, and Samir Mitragotri. "Polymer Backpack‐loaded Tissue Infiltrating Monocytes for Treating Cancer." Advanced Healthcare Materials (2024): 2304144. https://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.202304144
“Adoptive cell therapies are dramatically altering the treatment landscape of cancer. However, treatment of solid tumors remains a major unmet need, in part due to limited adoptive cell infiltration into the tumor and in part due to the immunosuppressive tumor microenvironment. The heterogeneity of tumors and presence of non-responders also calls for development of antigen-independent therapeutic approaches. Myeloid cells offer such an opportunity, given their large presence in the immunosuppressive tumor microenvironment, such as in triple negative breast cancer. However, their therapeutic utility is hindered by their phenotypic plasticity. Here, we leverage the impressive trafficking ability of adoptively transferred monocytes into the immunosuppressive 4T1 tumor to develop an anti-tumor therapy. To control monocyte differentiation in the tumor microenvironment, we developed surface-adherent “backpacks” stably modified with IFNγ to stimulate macrophage plasticity into a pro-inflammatory, anti-tumor phenotype, a strategy we refer to as Ornate Polymer-backpacks on Tissue Infiltrating Monocytes (OPTIMs). Treatment with OPTIMs substantially reduced tumor burden in a mouse 4T1 model and significant increased survival. Cytokine and immune cell profiling revealed that OPTIMs remodeled the tumor microenvironment into a pro-inflammatory state.”
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mPEG-PLGA from PolySciTech used in development of PARP/Kinase inhibitor drug delivery systems against cancer
Wednesday, March 27, 2024, 1:39 PM ET
There are a wide range of anticancer agents which prevent tumor growth by inhibiting cellular functions. PARP inhibitors, for example, prevent cancer cells from repairing strand breaks in their DNA structures leading to eventual cell death. Additionally, cyclin dependent kinase inhibitors prevent the cell from responding to DNA damage thus amplifying the effect of PARP inhibitors. Drugs based on interfering with the cellular operations of cancer cells can be effective at stopping tumor growth, but can also have serious side effects against healthy cells. Researchers at Northeastern University and Harvard Medical School used mPEG-PLGA (Cat# AK010) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create a nanoparticle delivery system combining the effects of a kinase inhibitor and a PARP inhibitor and tested the efficacy of this system against cancer cells. This research holds promise to provide for improved therapy against cancer in the future. Read more: Baldwin, Paige, Shicheng Yang, Adrienne Orriols, Sherrie Wang, Needa Brown, and Srinivas Sridhar. "A nano-cocktail of the PARP inhibitor talazoparib and CDK inhibitor dinaciclib for the treatment of triple negative breast cancer." Cancer Nanotechnology 15, no. 1 (2024): 1-16. https://cancer-nano.biomedcentral.com/articles/10.1186/s12645-023-00240-4
“The addition of the cyclin dependent kinase inhibitor (CDKi) dinaciclib to Poly-(ADP-ribose) polymerase inhibitor (PARPi) therapy is a strategy to overcome resistance to PARPi in tumors that exhibit homologous recombination (HR) deficiencies as well as to expand PARPi therapy to tumors that do not exhibit HR deficiencies. However, combination therapy using pathway inhibitors has been plagued by an inability to administer doses sufficient to achieve clinical benefit due to synergistic toxicities. Here we sought to combine nanoformulations of the PARPi talazoparib, nTLZ, and the CDKi dinaciclib, nDCB, in a nano-cocktail to enhance therapeutic efficacy while maintaining lower doses. Pharmacokinetics of nDCB were assessed to ensure it is compatible with nTLZ. nDCB was combined with nTLZ to generate a nano-cocktail nDCB:nTLZ, which elicits greater cell death in vitro compared to the combination of the free drugs. MDA-MB-231-LUC-D3H2LN xenografts were utilized to assess therapeutic efficacy of the nano-cocktail in terms of tumor progression. Administration of the nano-cocktail significantly slowed tumor progression in the HR proficient animal model compared to administration of free talazoparib and free dinaciclib at the same doses. Histology of the liver, spleen, and kidneys revealed long-term treatment did not induce nanoparticle associated morphological changes. Complete blood count did not reveal any significant hematologic changes after treatment with either the free combination or nano-cocktail. The efficacy and toxicity data suggest that further dose escalation can be pursued in order to achieve a stronger response. These data suggest the administration of combination therapy through the nano-cocktail leads to a better response than the use of free compounds and is a promising strategy for implementing combination therapy in the clinic.”
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PLGA from PolySciTech used in development of cartilage tissue regeneration for arthritis treatment
Friday, March 22, 2024, 4:36 PM ET
Arthritis is an inflammatory disease that affects about 1 in 5 USA adults (CDC National statistics). The immune system attacks cartilage in the joints which initially causes pain and stiffness but can lead to loss of functionality of the joint. Researchers at Universidade do Porto (Portugal) SINTEF Industry (Norway), Ulm University Medical Center Ulm (Germany), and Askel Healthcare Ltd (Finland) used PLGA from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop anti-inflammatory nanoparticles to work with a scaffold system for treatment of arthritis. This research holds promise to improve treatment of this debilitating disease. Read more: Pereira Vasconcelos, Daniela, Catarina Leite Pereira, Marina Couto, Estrela Neto, Beatriz Ribeiro, Filipe Albuquerque, Alexandra Freitas et al. "Nanoenabled Immunomodulatory Scaffolds for Cartilage Tissue Engineering." Advanced Functional Materials (2024): 2400627. https://onlinelibrary.wiley.com/doi/abs/10.1002/adfm.202400627
“Articular cartilage regeneration is a challenge in tissue engineering. Although diverse materials have been developed for this purpose, cartilage regeneration remains suboptimal. The integration of nanomaterials into 3D network materials holds great potential in the improvement of key mechanical properties, particularly important for osteochondral replacement scaffolds and even to function as carriers for disease-modifying drugs or other regulatory signals. In this study, a simple yet effective cell-free nanoenabled Col-PLA scaffold specially designed to enhance cartilage regeneration and modulate inflammatory response is proposed, by incorporating poly(lactic-co-glycolic acid) (PLGA) ibuprofen nanoparticles (NPs) into a collagen/polylactide (Col-PLA) matrix. The developed nanoenabled scaffold successfully decreases IL-1β release and leads to primary human chondrocytes survival, ultimately restoring extracellular matrix (ECM) production under inflammatory conditions. The nanoenabled Col-PLA scaffolds secretome effectively decreases macrophage invasion in vitro, as well as neutrophil infiltration and inflammatory mediators’, namely the complement component C5/C5a, C-reactive protein, IL-1β, MMP9, CCL20, and CXCL1/KC production in vivo in a rodent air-pouch model. Overall, the established nanoenabled scaffold has the potential to support chondrogenesis as well as modulate inflammatory response, overcoming the limitations of traditional tissue engineering strategies.”
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PLGA-Rhodamine from PolySciTech used in development of siRNA-loaded nanoparticles for Alzheimer's treatment.
Tuesday, March 19, 2024, 4:49 PM ET
Alzheimer’s disease is a chronic degenerative disorder characterized by deposition of extracellular amyloid plaques within the brain leading to cognitive decline. Researchers at Korea Institute of Science and Technology, Kyung Hee University, Chungnam National University, Catholic Kwandong University, Soonchunhyang University, and Seoul National University used PLGA-rhodamine (cat# AV027) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles to deliver siRNA. This research holds promise to improve treatment against Alzheimer’s disease. Read more: Shin, Hyo Jung, In Soo Kim, Seung Gyu Choi, Kayoung Lee, Hyewon Park, Juhee Shin, Dayoung Kim et al. "Rejuvenating aged microglia by p16ink4a-siRNA-loaded nanoparticles increases amyloid-β clearance in animal models of Alzheimer’s disease." Molecular Neurodegeneration 19, no. 1 (2024): 25. https://link.springer.com/article/10.1186/s13024-024-00715-x
“Age-dependent accumulation of amyloid plaques in patients with sporadic Alzheimer’s disease (AD) is associated with reduced amyloid clearance. Older microglia have a reduced ability to phagocytose amyloid, so phagocytosis of amyloid plaques by microglia could be regulated to prevent amyloid accumulation. Furthermore, considering the aging-related disruption of cell cycle machinery in old microglia, we hypothesize that regulating their cell cycle could rejuvenate them and enhance their ability to promote more efficient amyloid clearance. First, we used gene ontology analysis of microglia from young and old mice to identify differential expression of cyclin-dependent kinase inhibitor 2A (p16ink4a), a cell cycle factor related to aging. We found that p16ink4a expression was increased in microglia near amyloid plaques in brain tissue from patients with AD and 5XFAD mice, a model of AD. In BV2 microglia, small interfering RNA (siRNA)-mediated p16ink4a downregulation transformed microglia with enhanced amyloid phagocytic capacity through regulated the cell cycle and increased cell proliferation. To regulate microglial phagocytosis by gene transduction, we used poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles, which predominantly target microglia, to deliver the siRNA and to control microglial reactivity. Nanoparticle-based delivery of p16ink4a siRNA reduced amyloid plaque formation and the number of aged microglia surrounding the plaque and reversed learning deterioration and spatial memory deficits. We propose that downregulation of p16ink4a in microglia is a promising strategy for the treatment of Alzheimer’s disease. Keywords Alzheimer’s disease, Microglia senescence, Phagocytosis, p16ink4a, Cell cycle”
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Video: https://youtu.be/86Npj7uCigQ
PLGA from PolySciTech used in development of Ursolic acid delivery nanoparticles for treatment of breast cancer
Thursday, March 7, 2024, 11:33 AM ET
Breast cancer is the most common cancer in women in the United States accounting for approximately 30% of all new female cancers each year (American Cancer Society). Researchers at Mahidol University and Khon Kaen University (Thailand) used PLGA (Cat# AP059) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create and test the efficacy of chitosan-coated nanoparticles loaded with ursolic acid. This research holds promise to provide for improved cancer therapies in the future. Read more: Payomhom, Pattaree, Nattawadee Panyain, Chadamas Sakonsinsiri, Patompon Wongtrakoongate, Kornkamon Lertsuwan, Dakrong Pissuwan, and Kanlaya Prapainop Katewongsa. "Chitosan-Coated Poly (lactic-co-glycolic acid) Nanoparticles Loaded with Ursolic Acid for Breast Cancer Therapy." ACS Applied Nano Materials (2024). https://pubs.acs.org/doi/abs/10.1021/acsanm.3c06161
“Ursolic acid (UA), a pentacyclic triterpenoid found in various fruits and herbs, has the potential as an anticancer agent against multiple cancer types. Nevertheless, its clinical use was limited by its poor water solubility. To overcome this drawback, several nanocarriers were proposed to increase the bioavailability and efficacy of UA. However, the insights into the cellular targets and mechanisms of UA and UA nanoparticles (NPs) remain limited. In this study, chitosan-coated poly(lactic-co-glycolic acid) (PLGA/CS) NPs were loaded with UA. The obtained (UA)-PLGA/CS NPs were spherical with an approximate size of 250 nm and an encapsulation efficiency of 25%. Owing to their promising potential as drug carriers, the NPs were successfully delivered into breast cancer cells (MCF-7 and MDA-MB-231). Moreover, (UA)-PLGA/CS NPs enhanced the anticancer activity of UA, as evidenced by the IC50 values of 26.74 and 40.67 μM in MCF-7 and MDA-MB-231 cells, respectively. These values were lower than those of free UA (90.25 and 85.63 μM in MCF-7 and MDA-MB-231 cells, respectively). The improved cytotoxicity induced by (UA)-PLGA/CS NPs can be attributed to apoptosis induction, collective cell migration and invasion inhibition, and cell proliferation pathway disruption. These findings led to a better understanding of the anticancer effects and molecular mechanisms of (UA)-PLGA/CS NPs and their potential targets for breast cancer therapy. KEYWORDS: ursolic acid nanoparticles PLGA chitosan breast cancer”
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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a free scientific/networking conference hosted by Akina (http://bprconference.com/).
PEG-PLGA from PolySciTech used in the development of nanoparticles to deliver anti-tumor agents RG7388 and entinostat for cancer therapy
Thursday, February 22, 2024, 10:18 AM ET
In cancer therapy applications it is possible for specific drugs to work in concert creating a stronger effect than either of them would have on their own. Due to their interactions on several biological pathways, there is good indication that recently discovered RG7388 compound can work with entinostat to treat cancer. Researchers at Queen’s University Belfast and Al-Ahliyya Amman University used PEG-PLGA (Cat# AK010) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create and test the efficacy of nanoparticles loaded with both drugs. This research holds promise to improve cancer therapy in the future. Read more: Abed, Anas, Michelle K. Greene, Alhareth A. Alsa’d, Andrea Lees, Andrew Hindley, Daniel B. Longley, Simon S. McDade, and Christopher J. Scott. "Nanoencapsulation of MDM2 Inhibitor RG7388 and Class-I HDAC Inhibitor Entinostat Enhances their Therapeutic Potential Through Synergistic Antitumor Effects and Reduction of Systemic Toxicity." Molecular Pharmaceutics (2024). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.3c00926
“Inhibitors of the p53–MDM2 interaction such as RG7388 have been developed to exploit latent tumor suppressive properties in p53 in 50% of tumors in which p53 is wild-type. However, these agents for the most part activate cell cycle arrest rather than death, and high doses in patients elicit on-target dose-limiting neutropenia. Recent work from our group indicates that combination of p53–MDM2 inhibitors with the class-I HDAC inhibitor Entinostat (which itself has dose-limiting toxicity issues) has the potential to significantly augment cell death in p53 wild-type colorectal cancer cells. We investigated whether coencapsulation of RG7388 and Entinostat within polymeric nanoparticles (NPs) could overcome efficacy and toxicity limitations of this drug combination. Combinations of RG7388 and Entinostat across a range of different molar ratios resulted in synergistic increases in cell death when delivered in both free drug and nanoencapsulated formats in all colorectal cell lines tested. Importantly, we also explored the in vivo impact of the drug combination on murine blood leukocytes, showing that the leukopenia induced by the free drugs could be significantly mitigated by nanoencapsulation. Taken together, this study demonstrates that formulating these agents within a single nanoparticle delivery platform may provide clinical utility beyond use as nonencapsulated agents. KEYWORDS:cancer nanoparticles Entinostat nutlin toxicity combination therapy”
NEW: Corbion Purasorb® Polymers: https://akinainc.com/polyscitech/products/purasorb/
NEW: Ashland-TM products: https://akinainc.com/polyscitech/products/ashland/
BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a free scientific/networking conference hosted by Akina (http://bprconference.com/).
These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.14925503730774 seconds)
