Akina, Inc. is looking for a staff scientist to work on the research and development of biomedical, and pharmaceutical products and. The position is primarily formulations development, hydrogel research, and polymer chemistry. A bachelor’s degree in chemistry, biology, pharmaceutical sciences, biomedical engineering, or related scientific field is required. Prior work experience in research and development or pharmaceutical/biomedical field is a plus. Submit resume to General Manager, John Garner jg@akinainc.com

See more details here: http://akinainc.com/employment.php

Bacterial Keratitis (BK) is the leading cause of ocular infections leading to blindness. Although antibiotic eyedrops can be used for treatment these tend to have poor drug delivery due to loss through tears and other factors. Using a formulation which adheres to the mucosal layer of the eye can drastically improve drug delivery. Researchers at Birla Institute of Technology & Science-Pilani and LV Prasad Eye Institute use PLGA (cat# AP040) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create PLGA-chitosan conjugate particles. They used these to deliver antibiotic, moxifloxacin, in a nanoparticle formulation to provide improved drug uptake. This research holds promise to prevent blindness by treating ocular infections. Read more: Ch, Sanjay, Sri Ganga Padaga, Balaram Ghosh, Sanhita Roy, and Swati Biswas. "Chitosan-poly (lactide-co-glycolide)/poloxamer mixed micelles as a mucoadhesive thermo-responsive moxifloxacin eye drop to improve treatment efficacy in bacterial keratitis." Carbohydrate Polymers (2023): 120822. https://www.sciencedirect.com/science/article/pii/S0144861723002874

“Abstract: A mucoadhesive self-assembling polymeric system was developed to carry moxifloxacin (M) for treating bacterial keratitis (BK). Chitosan-PLGA (C) conjugate was synthesized, and poloxamers (F68/127) were mixed in different proportions (1: 5/10) to prepare moxifloxacin (M)-encapsulated mixed micelles (M@CF68/127(5/10)Ms), including M@CF68(5)Ms, M@CF68(10)Ms, M@CF127(5)Ms, and M@CF127(10)Ms. The corneal penetration and mucoadhesiveness were determined biochemically, in vitro using human corneal epithelial (HCE) cells in monolayers and spheroids, ex vivo using goat cornea, and in vivo via live-animal imaging. The antibacterial efficacy was studied on planktonic biofilms of P. aeruginosa and S. aureus (in vitro) and Bk-induced mice (in vivo). Both M@CF68(10)Ms and M@CF127(10)Ms demonstrated high cellular uptake, corneal retention, muco-adhesiveness, and antibacterial effect, with M@CF127(10)Ms exhibiting superior therapeutic effects in P. aeruginosa and S. aureus-infected BK mouse model by reducing the corneal bacterial load and preventing corneal damage. Therefore, the newly developed nanomedicine is promising for clinical translation in treating BK. Keywords: Chitosan Poloxamer Mixed micelles Bacterial keratitis Antibacterial Moxifloxacin”

Video: https://youtu.be/RngOUpdlpgE

Inflammatory Skin Conditions including eczema, seborrheic dermatitis, and psoriasis are extremely common and affect more than 27 million American adults. Ideally these can be treated using a localized or targeted therapy to reduce systemic side-effects. Researchers at Université Paris-Saclay, Université Paris-Cité, and Sorbonne Université (CNRS, Inserm, SFR-UMS-IPSIT) used PLGA-Rhodamine B (AV011) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create fluorescently traceable nanoparticles for stabilizing an emulsion. This research holds promise to provide for dual-drug loaded formulations for treatment of skin diseases. Read more: Beladjine, Mohamed, Claire Albert, Maxime Sintès, Ghozlene Mekhloufi, Claire Gueutin, Valérie Nicolas, Alexis Canette et al. "Pickering Emulsions Stabilized With Biodegradable Nanoparticles For The Co-Encapsulation Of Two Active Pharmaceutical Ingredients." International Journal of Pharmaceutics (2023): 122870. https://www.sciencedirect.com/science/article/pii/S0378517323002909

“Abstract: Innovative Pickering emulsions co-encapsulating two active pharmaceutical ingredients (API) were formulated for a topical use. An immunosuppressive agent, either cyclosporine A (CysA) or tacrolimus (TAC), was encapsulated at high drug loading in biodegradable and biocompatible poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP). These NP stabilized the oil droplets (Miglyol) containing an anti-inflammatory drug, calcitriol (CAL). The influence of the API on the physico-chemical properties of these emulsions were studied. Emulsions formulated with or without API had a similar macroscopic and microscopic structure, as well as interfacial properties, and they exhibited a good stability for at least 55 days. The emulsions did not alter the viability of human keratinocytes (HaCaT cell line) after 2 and 5 days of exposure to NP concentrations equivalent to efficient API dosages. Thus, these new Pickering emulsions appear as a promising multidrug delivery system for the treatment of chronical inflammatory skin diseases. Keywords: calcitriol co-encapsulation cyclosporine A interfacial properties nanoparticles Pickering emulsion PLGA tacrolimus skin diseases stability”


Video: https://youtu.be/aSx24hHnbdA

Even relatively minor ocular injuries can lead to downstream blindness due to localized inflammation and overgrowth of blood vessels occurring in response to the injury. This result can be prevented by TNF and VEGF inhibitors however this requires consistent application of the drugs during the healing process. Researchers at Harvard Medical School, Massachusetts Eye and Ear Infirmary, and University of New Mexico School of Medicine utilized PLGA-PEG-PLGA (AK141) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to develop a thermogel for long-acting delivery of adalimumab and aflibercept for ocular injection. This research holds promise to reduce the incidence of blindness by offering a new option for treatment of ocular damage. Read more: Zhou, Chengxin, Fengyang Lei, Pui-Chuen Hui, Natalie Wolkow, Claes Dohlman, Demetrios G. Vavvas, James Chodosh, and Eleftherios I. Paschalis. "A novel sustained release therapy of combined VEGF and TNF-α inhibitors leads to pan-ocular protection for months after severe ocular trauma." bioRxiv (2023): 2023-03. https://www.biorxiv.org/content/10.1101/2023.03.14.531626.abstract

“Purpose: To develop a clinically feasible and practical therapy for multi-ocular protection following ocular injury by using a thermosensitive drug delivery system (DDS) for sustained delivery of TNF-alpha and VEGF inhibitors to the eye. Methods: A thermosensitive, biodegradable hydrogel DDS (PLGA-PEG-PLGA triblock polymer) loaded with 0.7mg of adalimumab and 1.4 mg of aflibercept was injected subconjunctivally in Dutch-belted pigmented rabbits after corneal alkali injury. The polymer was tuned to transition from liquid to gel upon contact with body temperature without need of a catalyst. Control rabbits received 2mg of IgG loaded DDS or 1.4mg aflibercept loaded DDS. Animals were followed for 3 months and assessed for tolerability and prevention of corneal neovascularization (NV), improvement of corneal re-epithelialization, inhibition of retinal ganglion cell (RGC) and optic nerve axon loss, and inhibition of immune cell infiltration into the cornea. Drug release kinetics was assessed in vivo using aqueous humor protein analysis. Results: A single subconjunctival administration of dual anti-TNF-alpha/anti-VEGF DDS achieved sustained 3-month delivery of antibodies to the anterior chamber, iris, ciliary body, and retina. Administration after corneal alkali burn suppressed CD45+ immune cell infiltration into the cornea, completely inhibited cornea NV for 3 months, accelerated corneal re-epithelialization and wound healing, and prevented RGC and optic nerve axon loss at 3 months. In contrast, anti-VEGF alone or IgG DDS treatment led to persistent corneal epithelial defect, increased infiltration of CD45+ immune cells into the cornea, and significant loss of RGCs and optic nerve axons at 3 months. Aqueous humor protein analysis showed first-order release kinetics without adverse effects at the injection site. Conclusion: Sustained concomitant inhibition of TNF-alpha and VEGF using a biodegradable, slow-release thermosensitive DDS provides significant ocular protection and prevents corneal neovascularization and irreversible damage to retina and optic nerve after corneal alkali injury. This therapeutic approach has the potential to dramatically improve the outcomes of severe ocular injuries in patients.”

Video: https://youtu.be/l9PyjfDNJAk

Tissue engineering is a process where a cell scaffold or other structure is provided to allow for damaged or missing parts of the human body to regrow. The bioresorbable scaffold should match the mechanical properties of the tissue to be replaced as well as provide a surface for cells to attach to and grow on. Researchers at University of Missouri used PLCLs with a range of LA:CL ratios (cat# AP147, AP015, AP151, AP262) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to develop a mechanically robust and elastic heart valve replacement. This research holds promise to regrow or replace damaged portions of heart tissue. Read more: Snyder, Yuriy, and Soumen Jana. "Elastomeric Trilayer Substrates with Native-like Mechanical Properties for Heart Valve Leaflet Tissue Engineering." ACS Biomaterials Science & Engineering (2023). https://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.2c01430

“Heart valve leaflets have a complex trilayered structure with layer-specific orientations, anisotropic tensile properties, and elastomeric characteristics that are difficult to mimic collectively. Previously, trilayer leaflet substrates intended for heart valve tissue engineering were developed with nonelastomeric biomaterials that cannot deliver native-like mechanical properties. In this study, by electrospinning polycaprolactone (PCL) polymer and poly(l-lactide-co-ε-caprolactone) (PLCL) copolymer, we created elastomeric trilayer PCL/PLCL leaflet substrates with native-like tensile, flexural, and anisotropic properties and compared them with trilayer PCL leaflet substrates (as control) to find their effectiveness in heart valve leaflet tissue engineering. These substrates were seeded with porcine valvular interstitial cells (PVICs) and cultured for 1 month in static conditions to produce cell-cultured constructs. The PCL/PLCL substrates had lower crystallinity and hydrophobicity but higher anisotropy and flexibility than PCL leaflet substrates. These attributes contributed to more significant cell proliferation, infiltration, extracellular matrix production, and superior gene expression in the PCL/PLCL cell-cultured constructs than in the PCL cell-cultured constructs. Further, the PCL/PLCL constructs showed better resistance to calcification than PCL constructs. Trilayer PCL/PLCL leaflet substrates with native-like mechanical and flexural properties could significantly improve heart valve tissue engineering. KEYWORDS: elastomer electrospinning trilayer tissue engineering heart valve leaflet calcification”

Video: https://youtu.be/sO_s_RNSTJ8

Cardiovascular disease is the leading cause of all deaths worldwide. Restenosis is the re-narrowing of a blood vessel after catheterization and can lead to down-stream heart problems even after surgical intervention. Researchers at University of Virginia used PLGA-PEG-PLGA (cat# AK012) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create a thermogelling delivery vehicle for EED226 to deliver it in place in the periadventitial space of the injured artery and observe its effects. This research holds promise to further understand and prevent in-stent restenosis. Read more: Zhang, Mengxue, Jing Li, Qingwei Wang, Go Urabe, Runze Tang, Yitao Huang, Jose Verdezoto Mosquera et al. "Gene-repressing epigenetic reader EED unexpectedly enhances cyclinD1 gene activation." Molecular Therapy-Nucleic Acids (2023). https://www.cell.com/molecular-therapy-family/nucleic-acids/pdf/S2162-2531(23)00044-6.pdf

“Epigenetically switched, proliferative vascular smooth muscle cells (SMCs) form neointima, engendering stenotic diseases. Histone-3 lysine-27 trimethylation (H3K27me3) and acetylation (H3K27ac) marks are associated with gene repression and activation, respectively. The polycomb protein embryonic ectoderm development (EED) reads H3K27me3 and also enhances its deposition, hence a canonical gene-repressor. However, herein we found an unexpected role for EED in activating the bona fide pro-proliferative gene Ccnd1 (cyclinD1). EED overexpression in SMCs increased Ccnd1 mRNA, seemingly contradicting its gene-repressing function. Yet consistently, EED co-immunoprecipitated with gene-activating H3K27ac reader BRD4, and they co-occupied at both mitogen-activated Ccnd1 and mitogen-repressed P57 (bona fide anti-proliferative gene), as indicated by chromatin immunoprecipitation-qPCR. These results were abolished by an inhibitor of either the EED/H3K27me3 or BRD4/H3K27ac reader function. In accordance, elevating BRD4 increased H3K27me3. In vivo, while EED was upregulated in rat and human neointimal lesions, selective EED inhibition abated angioplasty-induced neointima and reduced cyclinD1 in rat carotid arteries. Thus, results uncover a previously unknown role of EED in Ccnd1 activation, likely via its cooperativity with BRD4 that enhances each other’s reader function, i.e. activating pro-proliferative Ccnd1 while repressing anti-proliferative P57. As such, this study confers mechanistic implications for the epigenetic intervention of neointimal pathology.”

Video: https://youtu.be/9_6b6nn1MR0

Ultrasound is a widely applicable and robust imaging technique that can determine internal features of humans in a non-invasive manner. One way to assist clinicians in treating cancer is to render the tumors visible by ultrasound so that they can be readily diagnosed and identified. Researchers at University of Illinois Urbana-Champaign Used PLGA (cat# AP154) as well as PLGA-PEG, and PLGA-PEG-Mal from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create targeted nanoparticles loaded with fluorescent dye and ultrasound contrast agent which attach to prostate cancer by ligand binding. This research holds promise to improve diagnostic techniques for treatment of cancer. Read More: Zhao, Shensheng, Leanne Lee, Yang Zhao, N. Liang, and Y. Chen. "Photoacoustic signal enhancement in dual-contrast gastrin-releasing peptide receptor-targeted nanobubbles." Frontiers in Bioengineering and Biotechnology 11 (2023). https://europepmc.org/article/pmc/pmc9887164

“Translatable imaging agents are a crucial element of successful molecular imaging. Photoacoustic molecular imaging relies on optical absorbing materials to generate a sufficient signal. However, few materials approved for human use can generate adequate photoacoustic responses. Here we report a new nanoengineering approach to further improve photoacoustic response from biocompatible materials. Our study shows that when optical absorbers are incorporated into the shell of a gaseous nanobubble, their photoacoustic signal can be significantly enhanced compared to the original form. As an example, we constructed nanobubbles using biocompatible indocyanine green (ICG) and biodegradable poly(lactic-co-glycolic acid) (PLGA). We demonstrated that these ICG nanobubbles generate a strong ultrasound signal and almost four-fold photoacoustic signal compared to the same concentration of ICG solution; our theoretical calculations corroborate this effect and elucidate the origin of the photoacoustic enhancement. To demonstrate their molecular imaging performance, we conjugated gastrin-releasing peptide receptor (GRPR) targeting ligands with the ICG nanobubbles. Our dual photoacoustic/ultrasound molecular imaging shows a more than three-fold enhancement in targeting specificity of the GRPR-targeted ICG nanobubbles, compared to untargeted nanobubbles or prostate cancer cells not expressing GRPR, in a prostate cancer xenograft mouse model in vivo. Keywords: cancer diagnosis, photoacoustic, ultrasound, molecular imaging, multimodal imaging, nanobubbles, GRPR, ICG”

Video: https://youtu.be/nXRUeyuLsoI

Pancreatic cancer is very difficult to treat and remains the leading cause of cancer-related deaths. Researchers at The Hebrew University of Jerusalem utilized PLGA-CY5 (cat# AV034) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create fluorescently traceable nanoparticles. They used these for testing the uptake of SiRNA loaded nanoparticles towards pancreatic cancer. This research holds promise to improve therapy against this fatal disease. Read More: Agbaria, Majd, Doaa Jbara-Agbaria, Etty Grad, Meital Ben-David-Naim, Gil Aizik, and Gershon Golomb. "Nanoparticles of VAV1 siRNA combined with LL37 peptide for the treatment of pancreatic cancer." Journal of Controlled Release 355 (2023): 312-326. https://www.sciencedirect.com/science/article/pii/S0168365923000937

Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of cancer-related death, and it is highly resistant to therapy owing to its unique extracellular matrix. VAV1 protein, overexpressed in several cancer diseases including pancreatic cancer (PC), increases tumor proliferation and enhances metastases formation, which are associated with decreased survival. We hypothesized that an additive anti-tumor effect could be obtained by co-encapsulating in PLGA nanoparticles (NPs), the negatively charged siRNA against VAV1 (siVAV1) with the positively charged anti-tumor LL37 peptide, as a counter-ion. Several types of NPs were formulated and were characterized for their physicochemical properties, cellular internalization, and bioactivity in vitro. NPs' biodistribution, toxicity, and bioactivity were examined in a mice PDAC model. An optimal siVAV1 formulation (siVAV1-LL37 NPs) was characterized with desirable physicochemical properties in terms of nano-size, low polydispersity index (PDI), neutral surface charge, high siVAV1 encapsulation efficiency, spherical shape, and long-term shelf-life stability. Cell assays demonstrated rapid engulfment by PC cells, a specific and significant dose-dependent proliferation inhibition, as well as knockdown of VAV1 mRNA levels and migration inhibition in VAV1+ cells. Treatment with siVAV1-LL37 NPs in the mice PDAC model revealed marked accumulation of NPs in the liver and in the tumor, resulting in an increased survival rate following suppression of tumor growth and metastases, mediated via the knockdown of both VAV1 mRNA and protein levels. This proof-of-concept study validates our hypothesis of an additive effect in the treatment of PC facilitated by co-encapsulating siVAV1 in NPs with LL37 serving a dual role as a counter ion as well as an anti-tumor agent.

Video: https://youtu.be/RdZzFuErcbk

Prostate cancer is the second most prevalent cause of cancer deaths in males, worldwide. There are many therapies available, however most patients with metastatic prostate cancer suffer relapse. Researchers at Barcelona Institute of Science and Technology, Institute for Advanced Chemistry of Catalonia (Spain), and Eindhoven University of Technology (Netherlands) used PLGA-PEG-Maleimide (cat# AI110) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to conjugate on WQP, a targeting peptide. They created nanoparticles and tested their ability to target towards prostate cells and provide treatment for prostate cancer. This research holds promise to improve therapy against prostate cancer in the future. Read More: Murar, Madhura, Silvia Pujals, and Lorenzo Albertazzi. "Multivalent effect of peptide functionalized polymeric nanoparticles towards selective prostate cancer targeting." Nanoscale Advances (2023). https://pubs.rsc.org/en/content/articlehtml/2023/na/d2na00601d

“The concept of selective tumor targeting using nanomedicines has been around for decades; however, no targeted nanoparticle has yet reached the clinic. A key bottleneck is the non-selectivity of targeted nanomedicines in vivo, which is attributed to the lack of characterization of their surface properties, especially the ligand number, thereby calling for robust techniques that allow quantifiable outcomes for an optimal design. Multivalent interactions comprise multiple copies of ligands attached to scaffolds, allowing simultaneous binding to receptors, and they play an important role in targeting. As such, ‘multivalent’ nanoparticles facilitate simultaneous interaction of weak surface ligands with multiple target receptors resulting in higher avidity and enhanced cell selectivity. Therefore, the study of weak binding ligands for membrane-exposed biomarkers is crucial for the successful development of targeted nanomedicines. Here we carried out a study of a cell targeting peptide known as WQP having weak binding affinity for prostate specific membrane antigen, a known prostate cancer biomarker. We evaluated the effect of its multivalent targeting using polymeric NPs over its monomeric form on the cellular uptake in different prostate cancer cell lines. We developed a method of specific enzymatic digestion to quantify the number of WQPs on NPs having different surface valencies and observed that increasing valencies resulted in a higher cellular uptake of WQP-NPs over the peptide alone. We also found that WQP-NPs showed higher uptake in PSMA over-expressing cells, attributed to a stronger avidity for selective PSMA targeting. This kind of strategy can be useful for improving the binding affinity of a weak ligand as a means for selective tumor targeting.”

Video: https://youtu.be/nnzHrU3gjlw

Sutures mechanically hold tissue closed in place so that wounds or surgical incisions can heal. They can also provide a platform for drug release or bioactive surface which can have additional therapeutic effects. Researchers at Balgrist University Hospital, ETH Zurich, and Cantonal Hospital Lucerne used PLGA (AP081) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create coated genipin-coated sutures for tendon repair. They applied this modified suture to repairing tendons which typically do not heal well after injury. This research holds promise to improve surgical repairs for traumatic injuries. Read more: Götschi, Tobias, Anne-Gita Scheibler, Patrick Jaeger, Karl Wieser, Claude Holenstein, Jess G. Snedeker, and Roland S. Camenzind. "Improved suture pullout through genipin-coated sutures in human biceps tendons with spatially confined changes in cell viability." Clinical Biomechanics (2023): 105907. https://www.sciencedirect.com/science/article/pii/S0268003323000384

“Highlights: Suture cut-through is a common cause of rotator cuff repair failure. Coating the suture with collagen cross-linker enhances strength of suture-tendon interface. Short-term in vitro culturing reduces tenocyte viability near suture. No difference in cell viability between treatment groups at 3 mm + from suture. Abstract: The suture-tendon interface often constitutes the point of failure in tendon suture repair. In the present study, we investigated the mechanical benefit of coating the suture with a cross-linking agent to strengthen the nearby tissue after suture placement in human tendons and we assessed the biological implications regarding tendon cell survival in-vitro. Freshly harvested human biceps long head tendons were randomly allocated to control (n = 17) or intervention (n = 19) group. According to the assigned group, either an untreated or a genipin-coated suture was inserted into the tendon. 24 h after suturing, mechanical testing composed of cyclic and ramp-to-failure loading was performed. Additionally, 11 freshly harvested tendons were used for short-term in vitro cell viability assessment in response to genipin-loaded suture placement. These specimens were analyzed in a paired-sample setting as stained histological sections using combined fluorescent/light microscopy. Tendons stitched with a genipin-coated suture sustained higher forces to failure. Cyclic and ultimate displacement of the tendon-suture construct remained unaltered by the local tissue crosslinking. Tissue crosslinking resulted in significant cytotoxicity in the direct vicinity of the suture (<3 mm). At larger distances from the suture, however, no difference in cell viability between the test and the control group was discernable. The repair strength of a tendon-suture construct can be augmented by loading the suture with genipin. At this mechanically relevant dosage, crosslinking-induced cell death is confined to a radius of <3 mm from the suture in the short-term in-vitro setting. These promising results warrant further examination in-vivo. Keywords: Tendon Suture Soft tissue repair Collagen crosslinking Mechanical testing Cell viability”

Video: https://youtu.be/GWGbUs5gaF4

Surgically placed implants can often develop bacterial infections which are difficult to treat by conventional antibiotics due to biofilm development. Researchers at Warsaw University of Technology and University of Amsterdam used PLGA (cat# AP041, AP081) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create antibiotic (vancomycin, rifampicin) loaded 3D printable constructs. This research holds promise to improve implant performance in the future. Read more: Martínez-Pérez, David, Clara Guarch-Pérez, Muhammad Abiyyu Kenichi Purbayanto, Emilia Choińska, Martijn Riool, Sebastian AJ Zaat, and Wojciech Święszkowski. "3D-printed dual drug delivery nanoparticleloaded hydrogels to combat antibiotic-resistant bacteria." International Journal of Bioprinting 9, no. 3 (2023). https://ijb.sg/index.php/int-j-bioprinting/article/view/683

“Implant-associated infections are not easy to diagnose and very difficult to treat, due to the ability of major pathogens, such as Staphylococcus aureus, to develop biofilms and escape the immune response and antibiotic treatment. We, therefore, aimed to develop a 3D-printed dual rifampicin (Rif)- and vancomycin (Van)-loaded polylacticco-glycolic acid (PLGA) nanoparticles (NPs) delivery system based on hydrogels made of gelatin methacrylate (GelMA). The release of Rif and Van from NPs manufactured from different PLGA molecular weights was studied in phosphate-buffered saline for 21 days. Low molecular weight PLGA NPs exhibited the fastest release of Rif and Van within the first 7 days and were selected for antimicrobial evaluation. Four different GelMA-based 3D-printed samples were successfully produced, carrying non-loaded NPs, Rif-NPs, Van-NPs, or alternating layers of Rif-NPs and Van-NP. The exposition of S. aureus against increased concentrations of Rif or Van produced new resistant strains to Rif (RifR) or Van (VanR). The GelMA hydrogel co-delivering Rif and Van eradicated S. aureus RN4220 RifR and RN4220 VanR strains. S. aureus RN4220 and S. aureus AMC 201 colonies developed resistance to Rif after contact with the GelMA hydrogel containing only Rif-NPs which appeared to be due to known mutations in the rpoB gene. In conclusion, 3D-printed GelMA hydrogel loaded with PLGA Rif-Van-NPs drug delivery system show promising in vitro results to prevent implant-associated infections caused by antimicrobial-resistant bacteria. Keywords: 3D printing; Antibiotic resistance; Staphylococcus aureus; Controlled drug delivery; Gelatin methacrylate; Nanoparticles”

Video: https://youtu.be/YxMk1KMdWjI

Ovarian cancer is a very common and lethal cancer which ranks fifth in cancer deaths amongst women (cancer.org). Recently, researchers at the City University of New York, Icahn School of Medicine at Mount Sinai, and Rudy Ruggles Research Institute used PLGA (cat# AP081) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create a pH-responsive nanoparticle with a PLGA-platinum core for treatment of ovarian cancer. This research holds promise to improve therapies against this often lethal disease. Read more: Wlodarczyk, Marek T., Sylwia A. Dragulska, Ying Chen, Mina Poursharifi, Maxier Acosta Santiago, John A. Martignetti, and Aneta J. Mieszawska. "Pt (II)-PLGA Hybrid in a pH-Responsive Nanoparticle System Targeting Ovarian Cancer." Pharmaceutics 15, no. 2 (2023): 607. https://www.mdpi.com/2130320

“Abstract: Platinum-based agents are the main treatment option in ovarian cancer (OC). Herein, we report a poly(lactic-co-glycolic acid) (PLGA) nanoparticle (NP) encapsulating platinum (II), which is targeted to a cell-spanning protein overexpressed in above 90% of late-stage OC, mucin 1 (MUC1). The NP is coated with phospholipid-DNA aptamers against MUC1 and a pH-sensitive PEG derivative containing an acid-labile hydrazone linkage. The pH-sensitive PEG serves as an off–on switch that provides shielding effects at the physiological pH and is shed at lower pH, thus exposing the MUC1 ligands. The pH-MUC1-Pt NPs are stable in the serum and display pH-dependent PEG cleavage and drug release. Moreover, the NPs effectively internalize in OC cells with higher accumulation at lower pH. The Pt (II) loading into the NP was accomplished via PLGA-Pt (II) coordination chemistry and was found to be 1.62 wt.%. In vitro screening using a panel of OC cell lines revealed that pH-MUC1-Pt NP has a greater effect in reducing cellular viability than carboplatin, a clinically relevant drug analogue. Biodistribution studies have demonstrated NP accumulation at tumor sites with effective Pt (II) delivery. Together, these results demonstrate a potential for pH-MUC1-Pt NP for the enhanced Pt (II) therapy of OC and other solid tumors currently treated with platinum agents. Keywords: nanoparticles; pH-sensitive; ovarian cancer; platinum therapy; in vivo imaging”

Video: https://youtu.be/lgf74nec28A

The human body will typically metabolize or excrete pharmaceutical substances limiting the action of any drug to a few hours to a day at most. One way to compensate for this is to load the drug into a biodegradable polymer which slowly releases it over a period of time. Recently, researchers at University of Cincinnati used PCL (AP011), PLA (AP006), PLGA 90:10 (AP049), and PLGA 50:50 (AP040) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create a series of dexamethasone loaded implants. These were tested for drug release and controlled delivery behavior. This research holds promise to improve long-acting injectables in the future. Read more: Zheng, Avery, Thomas Waterkotte, Tilahun Debele, Gregory Dion, and Yoonjee Park. "Biodegradable dexamethasone polymer capsule for long-term release." Korean Journal of Chemical Engineering 40, no. 2 (2023): 452-460. https://link.springer.com/article/10.1007/s11814-022-1358-y

“We have developed sustained Dex (dexamethasone) capsule implants for sustained local delivery for inflammatory disease treatment. Four different biodegradable polymers were used as capsule materials: polycaprolactone (PCL), poly(lactic acid) (PLA), 90:10 poly(lactic-co-glycolide) (PLGA), and 50:50 PLGA. The drug release profiles from the four types of capsule were compared and the profiles were fit to a cylindrical reservoir first-order kinetics model. As a result, 50:50 PLGA showed the fastest release with the largest permeability and partition coefficient at 0.4909 nm/s and 1.9519, respectively. On the other hand, PCL showed the slowest release with the smallest permeability and partition coefficient at 0.1915 nm/s and 0.8872, respectively. The results indicate that the drug release kinetics are highly correlated with hydrophobicity of the polymer sheet: the more hydrophobic, the slower the drug release kinetics for the hydrophilic drug. The in vitro therapeutic efficacy of the Dex implant was also explored using TNF-α stimulated human umbilical vein endothelial cells (HUVECs), showing effective suppression of IL-6 levels with the implant compared to free Dex with minimal toxicity. Overall, this study suggests that the release trend of Dex from implants follows the hydrophobicity of each polymer, and the Dex implant inhibits the IL-6 expression effectively.”

Video: https://youtu.be/7K_LdZyDU6g

The neurological experience of pain can vary widely and is controlled by a variety of factors in the brain. A classic example is when a person is cooking in a kitchen only to look down and realize that they were bleeding from a scratch on their hand that they didn’t even notice had happened. In this case a combination of distraction and activity suppressed the sensation of pain. To further understand the relationship between stress and pain management, researchers at Indian Institute of Science utilized PLGA (cat# AP041) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create clozapine N-oxide loaded microparticles for exploratory application of this agonist into the neural system as a way to control downstream processing of pain and stress experiences. This research holds promise to improve pain management therapies as well as further understanding of the workings of sensory processing in the brain. Read more: Barik, Arnab, Devanshi Shah, Pallavi Raj Sharma, and Rachit Agarwal. "The lateral septum plays a transforming role in acute stress-induced analgesia." bioRxiv (2023): 2023-01. https://www.biorxiv.org/content/biorxiv/early/2023/02/02/2023.01.30.526171.full.pdf

“Stress is a powerful modulator of pain. Specifically, acute stress due to physical restraint facilitates stress-induced analgesia (SIA). However, where, and how acute stress and pain pathways interface in the brain must be better understood. Here, we describe how the lateral septum (LS), a forebrain limbic nucleus, facilitates SIA through its downstream targets in the lateral hypothalamus (LH). We show that the LS→LH circuitry is sufficient to drive analgesia and is required for SIA. Further, we reveal that the LS→LH pathway is opioid-dependent and modulates pain through the pro-nociceptive neurons in the rostral ventromedial medulla (RVM). Remarkably, we found that the LS neurons are inhibitory, are recruited specifically when the mice struggle to escape under restraint, and, in turn, inhibit excitatory LH neurons. As a result, the RVM neurons downstream of LH are disengaged when the mice try to escape, thus suppressing nociception. Next, our data indicate that the efforts to escape are communicated by the lateral periaqueductal gray (lPAG) to the LS and activation of the upstream lPAG→LS circuit phenocopies LS→LH activation and results in analgesia. Thus, we have revealed a polysynaptic pathway that can transform escape behavior in mice under restraint to acute stress and resultant analgesia.”

Video: https://youtu.be/gngERZtmYoI

AKiNAfil™ 3D Printer Filament (https://akinainc.com/polyscitech/products/akinafil/) Biodegradable PLGA with controlled molecular weight and LA:GA ratio custom extruded into 1.7 or 2.8 mm sized filaments for use in 3D printing applications.

RiPurpose™ Olig1000-700 (https://akinainc.com/polyscitech/products/ripurpose/) recycled polyethylene terephthalate oligomer/Prepolymer for use in synthesis of many types of plastics both for biodegradable as well as commodity/industrial applications.

PolySciTech Cationic Polymers (https://akinainc.com/polyscitech/products/polyvivo/#CationizablePolymers) PLGA copolymers with cationic endcaps for delivery of nucleic acids including DNA/RNA for use in a wide range of genetic applications including vaccine and immunotherapy development.
Video: https://youtu.be/keK1bOHIxV0

Encapsulating drugs into nanoparticles requires that the drug be formulated in such a way that it prefers to be in the middle of the particle during emulsion formation. For hydrophobic drugs this is straightforward as these drugs have naturally poor solubility and prefer to be in the oil-soluble interior of polymeric particles. Hydrophilic drugs, however, are significantly more difficult as they tend to leave the nanoparticles during formation leading to poor drug loading. This phenomenon can be reduced by balancing the charges on a hydrophilic drug with a suitable counter charge on a relatively hydrophobic molecule, for example interacting a positively charged drug molecule with negatively charged palmitic acid. Recently, researchers From AstraZeneca and Purdue University used polylactide (cat# AP001) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create a series of nanoparticles using a wide array of counter-charge ions and tested these particles for their ability to encapsulate and release AZD2811. This research holds promise to improve the use of nanoparticles to carry a wide range of hydrophilic compounds. Read more: Dimiou, Savvas, James McCabe, Rebecca Booth, Jonathan Booth, Kalyan Nidadavole, Olof Svensson, Anders Sparén et al. "Selecting Counterions to Improve Ionized Hydrophilic Drug Encapsulation in Polymeric Nanoparticles." Molecular Pharmaceutics (2023). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.2c00855

“Hydrophobic ion pairing (HIP) can successfully increase the drug loading and control the release kinetics of ionizable hydrophilic drugs, addressing challenges that prevent these molecules from reaching the clinic. Nevertheless, polymeric nanoparticle (PNP) formulation development requires trial-and-error experimentation to meet the target product profile, which is laborious and costly. Herein, we design a preformulation framework (solid state screening, computational approach, and solubility in PNP-forming emulsion) to understand counterion−drug−polymer interactions and accelerate the PNP formulation development for HIP systems. The HIP interactions between a small hydrophilic molecule, AZD2811, and counterions with different molecular structures were investigated. Cyclic counterions formed amorphous ion pairs with AZD2811; the 0.7 pamoic acid/1.0 AZD2811 complex had the highest glass transition temperature (Tg; 162 °C) and the greatest drug loading (22%) and remained as phase-separated amorphous nanosized domains inside the polymer matrix. Palmitic acid (linear counterion) showed negligible interactions with AZD2811 (crystalline-free drug/counterion forms), leading to a significantly lower drug loading despite having similar log P and pKa with pamoic acid. Computational calculations illustrated that cyclic counterions interact more strongly with AZD2811 than linear counterions through dispersive interactions (offset π−π interactions). Solubility data indicated that the pamoic acid/AZD2811 complex has a lower organic phase solubility than AZD2811- free base; hence, it may be expected to precipitate more rapidly in the nanodroplets, thus increasing drug loading. Our work provides a generalizable preformulation framework, complementing traditional performance-indicating parameters, to identify optimal counterions rapidly and accelerate the development of hydrophilic drug PNP formulations while achieving high drug loading without laborious trial-and-error experimentation. KEYWORDS: in situ hydrophobic ion pairing, counterion−drug−polymer interactions, solid-state characterization, computational modeling, solubility measurements, polymeric nanoparticle formulation”

Video Link: https://youtu.be/PwF5tZ_GlLk

Due to their dual-nature of hydrophilicity and hydrophobicity, block copolymers have the capacity to spontaneously form nanoparticles under the correct conditions. The mechanism by which nanoparticles form is driven by a complex mixture of interfacial interactions and physics. The various conditions under which the particles form have a significant impact on the particles formulation and behavior. Recently, researchers at The University of Adelaide, The University of Queensland (Australia), Zhejiang University (China) and Harvard University (USA) used PEG-PLGA (cat# AK010 and AK026), PEG-PLA (cat# AK168), and mPEG-PCL (cat# AK128) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create nanoparticles under controlled conditions and evaluated these in response to loading of model drugs and particle behavior. This research holds promise to improve the controlled formation of nanoparticles in the future. Read more: Yang, Guangze, Yun Liu, Song Jin, Yue Hui, Xing Wang, Letao Xu, Dong Chen, David Weitz, and Chun‐Xia Zhao. "Phase separation‐induced nanoprecipitation for making polymer nanoparticles with high drug loading." Aggregate: e314. https://onlinelibrary.wiley.com/doi/abs/10.1002/agt2.314

“Increasing drug loading remains a critical challenge in the development and translation of nanomedicine. High drug-loading nanoparticles have demonstrated unique advantages such as less carrier material used, better-controlled drug release, and improved efficacy and safety. Herein, we report a simple and efficient salt concentration screening method for making polymer nanoparticles with exceptionally high drug loading (up to 66.5 wt%) based on phase separation-induced nanoprecipitation. Upon addition of salt, phase separation occurs in a miscible solvent-water solution delaying the precipitation time of drugs and polymers to different extents, facilitating their co-precipitation thus the formation of high drug-loading nanoparticles with high encapsulation efficiency (>90%) and excellent stability (>1 month). This technology is versatile and easy to be adapted to various hydrophobic drugs, different polymers, and solvents. This salt-induced nanoprecipitation strategy offers a novel approach to fabricating polymer nanoparticles with tunable drug loading, and opens great potentials for future nanomedicines. KEYWORDS drug loading, liquid-liquid phase separation, nanoparticles, nanoprecipitation, salt”

Video link: https://youtu.be/XTgAtYMVEq4

In partnership with RiKarbon, PolySciTech division of Akina, Inc. is offering PET oligomeric precursor (RiPurposeTM, Patent pending # 63/312519) (https://akinainc.com/polyscitech/products/ripurpose/index.php) This versatile precursor can be utilized in a wide array of reactions. Unlike carboxytelechelic (which only has terminal carboxylic acid groups) or hydroxytelechelic (only has terminal alcohol groups) RiPurpose contains both functional end-groups allowing for direct reactions with a variety of comonomers to directly form plastic groups. Find out more and obtain a sample to test out your ideas with at PolySciTech.

Much still remains to be learned about how nanoparticles interact with cells and living systems. Due to the small size of nanoparticles (typically ~0.1 – 1 µm, < 1% the size of a typical human cell at 100 µm) they have the ability to transfer into cells or interact with surface proteins to elicit desired responses. Researchers at Hacettepe University and Süleyman Demirel University (Turkey) used fluorescently labelled mPEG-PLGA-FKR560 (AV021) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create labelled nanoparticles with controlled shape profiles. They investigated the effects of shape on drug release, cell interactions, and biodistribution. This research holds promise to improve the utilization of nanoparticles for disease treatment. Read more: Kaplan, Meryem, Kıvılcım Öztürk, Süleyman Can Öztürk, Ece Tavukçuoğlu, Güneş Esendağlı, and Sema Calis. "Effects of Particle Geometry for PLGA-Based Nanoparticles: Preparation and In Vitro/In Vivo Evaluation." Pharmaceutics 15, no. 1 (2023): 175. https://www.mdpi.com/article/10.3390/pharmaceutics15010175

“Abstract: The physicochemical properties (size, shape, zeta potential, porosity, elasticity, etc.) of nanocarriers influence their biological behavior directly, which may result in alterations of the therapeutic outcome. Understanding the effect of shape on the cellular interaction and biodistribution of intravenously injected particles could have fundamental importance for the rational design of drug delivery systems. In the present study, spherical, rod and elliptical disk-shaped PLGA nanoparticles were developed for examining systematically their behavior in vitro and in vivo. An important finding is that the release of the encapsulated human serum albumin (HSA) was significantly higher in spherical particles compared to rod and elliptical disks, indicating that the shape can make a difference. Safety studies showed that the toxicity of PLGA nanoparticles is not shape dependent in the studied concentration range. This study has pioneering findings on comparing spherical, rod and elliptical disk-shaped PLGA nanoparticles in terms of particle size, particle size distribution, colloidal stability, morphology, drug encapsulation, drug release, safety of nanoparticles, cellular uptake and biodistribution. Nude mice bearing non-small cell lung cancer were treated with 3 differently shaped nanoparticles, and the accumulation of nanoparticles in tumor tissue and other organs was not statistically different (p > 0.05). It was found that PLGA nanoparticles with 1.00, 4.0 ± 0.5, 7.5 ± 0.5 aspect ratios did not differ on total tumor accumulation in non-small cell lung cancer. Keywords: nanoparticles; particle shape; anisotrop; human serum albumin; cellular uptake; biodistribution; drug delivery; PLGA”

Video: https://youtu.be/XvyUtcuQO-g

As a means to prevent stroke, Carotid Endarterectomy is commonly performed to improve the vessel condition for transporting blood to the brain. However, there is significant risk with this procedure of the vessel reclosing or other complications. A better option is to utilize a scaffold which will allow for the growth of a wider vessel to repair or replace the damaged one. Recently, researchers at Universitas Airlangga (Indonesia) used PLLA (Cat# AP006) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create a composite mesh for vessel repair. This research holds promise to improve treatment of vascular diseases. Read More: Salsabila, Dhea Saphira, Prihartini Widiyanti, Edric Hernando, Indira Maretta Hulu, and Tarissa Diandra Putri Wibowo. "Characterization of Coaxially Electrospun Poly (L-Lactic) Acid/Chitosan with Heparin Modification as Patch Angioplasty Candidate." Journal of Membrane Science and Research 9, no. 1 (2023). http://www.msrjournal.com/&url=http:/www.msrjournal.com/article_699986.html

“Atherosclerosis in the carotid artery is the leading cause of ischemic stroke. Carotid Endarterectomy (CEA) is a procedure of atherosclerosis plaque removal to prevent stenosis, which significantly reduces the risk of transient ischemic attack. Currently, the application of commercialized patch grafts in CEA has shown several disadvantages regarding its incompatibility with the carotid artery. Poly (L-Lactic) Acid (PLLA)/Chitosan (CS) electrospun fibers with heparin modification were fabricated as biocompatible patch graft through coaxial electrospinning with composition variations of 1:0; 1:2; 1:3; 1:4. Pre-synthesis measurement of viscosity and surface tension was conducted to optimize the electrospinnability of PLLA 10% and CS 3% (w/v). FTIR results confirmed the existence of each material's functional group. Physical and mechanical properties were enhanced along with the increased PLLA/CS ratio. The hydrophilicity was optimized by the 1:4 electrospun fibers, which reduced the contact angle to 27°. The 1:4 electrospun fibers also resulted in a suitable degradation rate within 72 days and desirable tensile strength at 3.864 with 24.8% elongation. According to the results, Poly (L-Lactic) Acid/Chitosan electrospun fibers have a promising potential as a patch angioplasty candidate”

Video: https://youtu.be/i9SY5aS8x10

Antimicrobial resistance creates a significant barrier to treatment of bacterial infection. SET-M33, a non-natural antimicrobial peptide, can be used for treatment of cystic fibrosis however requires a delivery mechanism to provide it to the appropriate location in the lung tissue. Recently researchers at University of Siena, SetLance srl, University of Campania, and University of Naples used PLGA-Rhodamine (Cat # AV011) from PolySciTech division of Akina, Inc. (www.polyscitech.com) in development of an SET-M33 delivery nanoparticle. This research holds promise to improve treatment of lung-bacterial infections. Read more: Cresti, Laura, Gemma Conte, Giovanni Cappello, Jlenia Brunetti, Chiara Falciani, Luisa Bracci, Fabiana Quaglia, Francesca Ungaro, Ivana d’Angelo, and Alessandro Pini. "Inhalable Polymeric Nanoparticles for Pulmonary Delivery of Antimicrobial Peptide SET-M33: Antibacterial Activity and Toxicity In Vitro and In Vivo." Pharmaceutics 15, no. 1 (2023): 3. https://www.mdpi.com/2017528

“Abstract: Development of inhalable formulations for delivering peptides to the conductive airways and shielding their interactions with airway barriers, thus enhancing peptide/bacteria interactions, is an important part of peptide-based drug development for lung applications. Here, we report the construction of a biocompatible nanosystem where the antimicrobial peptide SET-M33 is encapsulated within polymeric nanoparticles of poly(lactide-co-glycolide) (PLGA) conjugated with polyethylene glycol (PEG). This system was conceived for better delivery of the peptide to the lungs by aerosol. The encapsulated peptide showed prolonged antibacterial activity, due to its controlled release, and much lower toxicity than the free molecule. The peptide-based nanosystem killed Pseudomonas aeruginosa in planktonic and sessile forms in a dose-dependent manner, remaining active up to 72 h after application. The encapsulated peptide showed no cytotoxicity when incubated with human bronchial epithelial cells from healthy individuals and from cystic fibrosis patients, unlike the free peptide, which showed an EC50 of about 22 µM. In vivo acute toxicity studies in experimental animals showed that the peptide nanosystem did not cause any appreciable side effects, and confirmed its ability to mitigate the toxic and lethal effects of free SET-M33. Keywords: polymeric nanoparticles; lung delivery; inhalable formulations; nanoparticle properties; aerosolization; nanoparticle/mucus interactions; antimicrobial peptides; antimicrobial resistance; Pseudomonas aeruginosa”



Video: https://youtu.be/looWDKpAwFY

Unlike most organs in the human body, the brain has a significant barrier against uptake of medicinal compounds present in the blood. Crossing this barrier is difficult for anything other than small, hydrophobic molecules and is particularly challenging for nanoparticles. This barrier is poorly understood and the exact features and properties of a particle which allow it to either pass or, not pass, through the barrier has not been fully characterized. Researchers at Massachusetts Institute of Technology used PLGA-CY5 (cat# AV034) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create fluorescently trackable nanoparticles. They tested these particles with a variety of configurations and surface chemistries against model brain barrier systems to further understand what properties control this transport. This research holds promise to improve delivery of therapeutics to the brain in the future. Read more: Lamson, Nicholas G., Andrew J. Pickering, Jeffrey Wyckoff, Priya Ganesh, Joelle P. Straehla, and Paula T. Hammond. "Core material and surface chemistry of Layer-by-Layer (LbL) nanoparticles independently direct uptake, transport, and trafficking in preclinical blood-brain barrier (BBB) models." bioRxiv (2022). https://www.biorxiv.org/content/10.1101/2022.10.31.514595.abstract

“Development of new treatments for neurological disorders, especially brain tumors and neurodegenerative diseases, is hampered by poor accumulation of new therapeutic candidates in the brain. Drug carrying nanoparticles are a promising strategy to deliver therapeutics, but there is a major need to understand interactions between nanomaterials and the cells of the blood-brain barrier (BBB), and to what degree these interactions can be predicted by preclinical models. Here, we use a library of eighteen layer-by-layer electrostatically assembled nanoparticles (LbL-NPs) to independently assess the impact of nanoparticle core stiffness and surface chemistry on in vitro uptake and transport in three common assays, as well as intracellular trafficking in hCMEC/D3 endothelial cells. We demonstrate that nanoparticle core stiffness impacts the magnitude of material transported, while surface chemistry influences how the nanoparticles are trafficked within the cell. Finally, we demonstrate that these factors similarly dictate in vivo BBB transport using intravital imaging through cranial windows in mice, and we discover that a hyaluronic acid surface chemistry provides an unpredicted boost to transport. Taken together, these findings highlight the importance of considering factors such as assay geometry, nanomaterial labelling strategies, and fluid flow in designing preclinical assays to improve nanoparticle screening throughput for drug delivery to the brain.”

See Video: https://youtu.be/fAHFUmqonmc

Targeted drug delivery in a living body can be achieved by applying a non-invasive ‘trigger’ which creates a change in the delivery carrier that releases the medicinal compound from the system. This can be done by using low intensity ultrasound which can cause nanoparticles to release their payload of medicine at the location where the ultrasound is focused. Researchers at University of Utah used mPEG-PLA (Cat# AK009) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles that can be triggered by ultrasound to release on demand. This research holds promise to provide for controlled, localized drug delivery. Read more: Wilson, Matthew G., Aarav Parikh, and Jan Kubanek. "Effective ultrasound-triggered drug release from stable nanocarriers." bioRxiv (2022): 2021-12. https://www.biorxiv.org/content/10.1101/2021.12.14.471689.abstract

“Abstract: Selective delivery of concentrated medication into specified targets would realize the promise of effective personalized medicine with minimal side effects. Low-intensity ultrasound provides noninvasive and practical means to deliver drugs from nanocarriers selectively into its focus. However, which nanocarriers and ultrasound parameters can provide effective and safe drug delivery has been unclear. We found that nanocarriers with highly stable perfluorocarbon cores mediate effective release so long as they are activated by ultrasound of relatively low frequencies. We further demonstrated a repeatable method for manufacturing these nanocarriers to help facilitate future work in this area. This study guides the formulation and release parameters for effective and safe drug delivery into specific parts of the body or brain regions.”

See Video: https://youtu.be/8G2X1pIc2sg

Bacterial infection often prevents and delays healing in wounds. Antimicrobial peptides can provide for treatment of infections, however these are quickly degraded and become inactive in vivo. One strategy to provide for the delivery of these peptides is to conjugate them onto the surface of nanoparticles. Researchers at Universidade do Porto and Universidade Católica do Porto (Portugal) used PLGA-PEG-Mal (Cat# AI110) and mPEG-PLGA (Cat# AK102) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles functionalized with antimicrobial peptides for treatment of bacterial infections. This research holds promise to improve therapies against wound infections. Read more: Ramôa, António Miguel, Filipa Campos, Luís Moreira, Cátia Teixeira, Victoria Leiro, Paula Gomes, José das Neves, M. Cristina L. Martins, and Cláudia Monteiro. "Antimicrobial peptide-grafted PLGA-PEG nanoparticles to fight bacterial wound infections." Biomaterials Science (2023). https://pubs.rsc.org/en/content/articlehtml/2023/bm/d2bm01127a

“Abstract: Wound infection treatment with antimicrobial peptides (AMPs) is still not a reality, due to the loss of activity in vivo. Unlike the conventional strategy of encapsulating AMPs on nanoparticles (NPs) leaving activity dependent on the release profile, this work explores AMP grafting to poly(D,L-lactide-co-glycolide)-polyethylene glycol NPs (PLGA-PEG NPs), whereby AMP exposition, infection targeting and immediate action are promoted. NPs are functionalized with MSI-78(4–20), an equipotent and more selective derivative of MSI-78, grafted through a thiol-maleimide (Mal) Michael addition. NPs with different ratios of PLGA-PEG/PLGA-PEG-Mal are produced and characterized, with 40%PLGA-PEG-Mal presenting the best colloidal properties and higher amounts of AMP grafted as shown by surface charge (+8.6 ± 1.8 mV) and AMP quantification (326 μg mL−1, corresponding to 16.3 μg of AMP per mg of polymer). NPs maintain the activity of the free AMP with a minimal inhibitory concentration (MIC) of 8–16 μg mL−1 against Pseudomonas aeruginosa, and 16–32 μg mL−1 against Staphylococcus aureus. Moreover, AMP grafting accelerates killing kinetics, from 1–2 h to 15 min for P. aeruginosa and from 6–8 h to 0.5–1 h for S. aureus. NP activity in a simulated wound fluid is maintained for S. aureus and decreases slightly for P. aeruginosa. Furthermore, NPs do not demonstrate signs of cytotoxicity at MIC concentrations. Overall, this promising formulation helps unleash the full potential of AMPs for the management of wound infections.”

See Video: https://youtu.be/_x6MYzpzmVU