PolySciTech™ - Technical Blog

Technical Blog

John Garner, General Manager

A blog dedicated to answering technical questions in an open format relating to products from PolySciTech, a division of Akina, Inc.

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Extrusion Process Optimization Research Performed Using Ashland PLGA Available for Distribution through PolySciTech

Tuesday, November 12, 2024, 3:57 PM ET

Through a partnership with Ashland, PolySciTech provides distribution of PLGA products for non-clinical development purposes (https://akinainc.com/polyscitech/products/ashland/). Recently several of these polymers were utilized in research on hot-melt extrusion processing for development of long-acting implants. This research holds promise to provide for LAIs that can achieve desired drug release profiles for long-term patient care. Read more: Yang, Fengyuan, Ryan Stahnke, Kamaru Lawal, Cory Mahnen, Patrick Duffy, Shuyu Xu, and Thomas Durig. "Development of poly (lactic-co-glycolic acid)(PLGA) based implants using hot melt extrusion (HME) for sustained release of drugs: The impacts of PLGA’s material characteristics." International Journal of Pharmaceutics 663 (2024): 124556. https://www.sciencedirect.com/science/article/pii/S0378517324007907

“Hot melt extrusion (HME) processed Poly (lactic-co-glycolic acid) (PLGA) implant is one of the commercialized drug delivery products, which has solid, well-designed shape and rigid structures that afford efficient locoregional drug delivery on the spot of interest for months. In general, there are a variety of material, processing, and physiological factors that impact the degradation rates of PLGA-based implants and concurrent drug release kinetics. The objective of this study was to investigate the impacts of PLGA’s material characteristics on PLGA degradation and subsequent drug release behavior from the implants. Three model drugs (Dexamethasone, Carbamazepine, and Metformin hydrochloride) with different water solubility and property were formulated with different grades of PLGAs possessing distinct co-polymer ratios, molecular weights, end groups, and levels of residual monomer (high/ViatelTM and low/ ViatelTM Ultrapure). Physicochemical characterizations revealed that the plasticity of PLGA was inversely proportional to its molecular weight; moreover, the residual monomer could impose a plasticizing effect on PLGA, which increased its thermal plasticity and enhanced its thermal processability. Although the morphology and microstructure of the implants were affected by many factors, such as processing parameters, polymer and drug particle size and distribution, polymer properties and polymer-drug interactions, implants prepared with ViatelTM PLGA showed a smoother surface and a stronger PLGA-drug intimacy than the implants with ViatelTM Ultrapure PLGA, due to the higher plasticity of the ViatelTM PLGA. Subsequently, the implants with ViatelTM PLGA exhibited less burst release than implants with ViatelTM Ultrapure PLGA, however, their onset and progress of the lag and substantial release phases were shorter and faster than the ViatelTM Ultrapure PLGA-based implants, owing to the residual monomer accelerated the water diffusion and autocatalyzed PLGA hydrolysis. Even though the drug release profiles were also influenced by other factors, such as composition, drug properties and polymer-drug interaction, all three cases revealed that the residual monomer accelerated the swelling and degradation of PLGA and impaired the implant’s integrity, which could negatively affect the subsequent drug release behavior and performance of the implants. These results provided insights to formulators on rational PLGA implant design and polymer selection.”

NEW: Ashland-TM products: https://akinainc.com/polyscitech/products/ashland/

Video: https://youtu.be/h2JEHB5Uvz0

mPEG-PLGA from PolySciTech used in development of mRNA delivery system for cancer therapy.

Tuesday, November 5, 2024, 4:09 PM ET

The ability to deliver mRNA to cells enable direct formation of desired therapeutic or immune-controlling proteins at the cells directly. This has previously been used as part of the covid vaccine though the technique can also be used for therapies against cancer as well. Researchers at University of Ottawa used mPEG-PLGA (cat# AK010) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop particles to deliver mRNA to tumor cells. This research holds promise to provide for further treatment options for cancer in the future. Read more: El-Sahli, Sara, Shireesha Manturthi, Emma Durocher, Yuxia Bo, Alexandra Akman, Christina Sannan, Melanie Kirkby et al. "Nanoparticle-mediated mRNA delivery to TNBC PDX tumors." (2024). https://www.researchsquare.com/article/rs-4892937/latest

“mRNA-based therapies can overcome several challenges faced by traditional therapies in treating a variety of diseases by selectively modulating genes/proteins without genomic integration. However, due to mRNA’s poor stability and inherent limitations, nanoparticle (NP) platforms have been developed to deliver functional mRNA into cells. In cancer treatment, mRNA technology has multiple applications, such as restoration of tumor suppressors and activating anti-tumor immunity. Most of these applications have been evaluated using simple cell line-based tumor models, which failed to represent the complexity, heterogeneity, and 3D architecture of patient tumors. This discrepancy has led to inconsistencies and failures in clinical translation. Compared to cell line models, Patient-derived xenograft (PDX) models more accurately represent patient tumors and are better suitable for modeling. Therefore, for the first time, this study employed two different TNBC PDX tumors to examine the effects of mRNA-NPs. mRNA-NPs are developed using EGFP-mRNA as a model and studied in TNBC cell lines, ex vivo TNBC PDX organotypic slice cultures, and in vivoTNBC PDX tumors. Our findings show that NPs can effectively accumulate in tumors after intravenous administration, protecting and delivering mRNA to PDX tumors with different genetic and chemosensitivity backgrounds. These studies offer more clinically relevant modeling systems for mRNA nanotherapies for cancer applications.”

mPEG-PLGA (Cat# AK010): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AK010#h

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PLGA-Rhodamine from PolySciTech used in development of CBD and BDNF brain delivery system for treatment of Alzheimer's

Friday, October 25, 2024, 4:10 PM ET

Alzheimer’s disease is a chronic, degenerative condition which leads to memory loss. Researchers at North Dakota State University used PLGA-Rhodamine (AV011) and PLGA (AP018) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles targeting the brain. These were used for the delivery of Cannabidiol (CBD) (anti-inflammatory) and brain-derived neurotrophic factor (BDNF). This research holds promise to provide for treatment against Alzheimer’s disease. Read more: Mahanta, Arun Kumar, Bivek Chaulagain, Riddhi Trivedi, and Jagdish Singh. "Mannose-Functionalized Chitosan-Coated PLGA Nanoparticles for Brain-Targeted Codelivery of CBD and BDNF for the Treatment of Alzheimer’s Disease." ACS Chemical Neuroscience (2024). https://pubs.acs.org/doi/abs/10.1021/acschemneuro.4c00392

“Alzheimer’s disease (AD) is a common neurodegenerative disease causing cognitive and memory decline. AD is characterized by the deposition of amyloid-β and hypophosphorylated forms of tau protein. AD brains are found to be associated with neurodegeneration, oxidative stress, and inflammation. Cannabidiol (CBD) shows neuroprotective, antioxidant, and anti-inflammatory properties and simultaneously reduces amyloid-β production and tau hyperphosphorylation. The brain-derived neurotrophic factor (BDNF) plays a vital role in the development and maintenance of the plasticity of the central nervous system. A decline of BDNF levels in AD patients results in reduced plasticity and neuronal cell death. Current therapeutics against AD are limited to only symptomatic relief, necessitating a therapeutic strategy that reverses cognitive decline. In this scenario, combination therapy of CBD and BDNF could be a fruitful strategy for the treatment of AD. We designed mannose-conjugated chitosan-coated poly(d,l-lactide-co-glycolide (PLGA) (CHTMAN-PLGA) nanoparticles for the codelivery of CBD and BDNF to the brain. Chitosan is modified with mannose to specifically target the glucose transporter-1 (GLUT-1) receptor abundantly present in the blood–brain barrier for selectively delivering therapeutics to the brain. The CBD-encapsulated nanoparticles showed an average hydrodynamic diameter of 306 ± 8.12 nm and a zeta potential of 31.7 ± 1.53 mV. The coated nanoparticles prolonged encapsulated CBD release from the PLGA matrix. The coated nanoparticles exhibited sustained release of CBD for up to 22 days with 91.68 ± 2.91% release of the encapsulated drug. The coated nanoparticles, which had a high positive zeta potential (31.7 ± 1.53 mV), encapsulated the plasmid DNA. The qualitative transfection efficiency was investigated using CHTMAN-PLGA-CBD/pGFP in bEND.3, primary astrocytes, and primary neurons, while the quantitative transfection efficiency of the delivery system was determined using CHTMAN-PLGA-CBD/pBDNF. In vitro, the pBDNF transfection study revealed that the BDNF expression was 4-fold higher for CHTMAN-PLGA-CBD/pBDNF than for naked pBDNF in all of the cell lines. The cytotoxicity and hemocompatibility of the designed nanoparticles were tested in bEND.3 cells and red blood cells, respectively, and the nanoparticles were found to be nontoxic and hemocompatible. Hence, mannose-conjugated chitosan-coated PLGA nanoparticles could be useful as brain-targeting delivery vehicles for the codelivery of CBD and BDNF for possible AD treatment.”

PLGA-Rhodamine (Cat# AV011): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AV011#h

PLGA (Cat# AP018): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AP018#h

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mPEG-PLA from PolySciTech used in development of phototherapy treatment of cancer.

Friday, October 25, 2024, 4:09 PM ET

A common problem with chemotherapy is the non-specific delivery of drugs to healthy cells which causes systemic side effects. Phototherapy uses a combination of an injectable formulation with an illumination trigger applied to the site of the tumor. The formulation remains relatively inert until it interacts with the light to deliver the drug. Researchers at The State University of New York used mPEG-PLA (AK009) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles which can be triggered to release paclitaxel upon exposure to illumination. This research holds promise to provide treatment of cancer in the future. Read more: Giram, Prabhanjan, Ganesh Bist, Sukyung Woo, Elizabeth Wohlfert, Roberto Pili, and Youngjae You. "Prodrugs of paclitaxel improve in situ photo‐vaccination." Photochemistry and Photobiology (2024). https://onlinelibrary.wiley.com/doi/abs/10.1111/php.14025

“Abstract: Photodynamic therapy (PDT) effectively kills cancer cells and initiates immune responses that promote anticancer effects locally and systemically. Primarily developed for local and regional cancers, the potential of PDT for systemic antitumor effects [in situ photo-vaccination (ISPV)] remains underexplored. This study investigates: (1) the comparative effectiveness of paclitaxel (PTX) prodrug [Pc-(L-PTX)2] for PDT and site-specific PTX effects versus its pseudo-prodrug [Pc-(NCL-PTX)2] for PDT combined with checkpoint inhibitors; (2) mechanisms driving systemic antitumor effects; and (3) the prophylactic impact on preventing cancer recurrence. A bilateral tumor model was established in BALB/c mice through subcutaneous injection of CT26 cells. Mice received the PTX prodrug (0.5 μmole kg−1, i.v.), and tumors were treated with a 690-nm laser (75 mW cm−2 for 30 min, drug-light interval 0.5 h, light does 135 J cm−1), followed by anti-CTLA-4 (100 μg dose−1, i.p.) on days 1, 4, and 7. Notable enhancement in both local and systemic antitumor effectiveness was observed with [Pc-(L-PTX)2] compared to [Pc-(NCL-PTX)2] with checkpoint inhibitor. Immune cell depletion and immunohistochemistry confirmed neutrophils and CD8+ T cells are effectors for systemic antitumor effects. Treatment-induced immune memory resisted newly rechallenged CT26, showcasing prophylactic benefits. ISPV with a PTX prodrug and anti-CTLA-4 is a promising approach for treating metastatic cancers and preventing recurrence.”

mPEG-PLA (Cat# AK009): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AK009#h

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PLGA-PEG-COOH from Akina used in development of nanoparticles for drug delivery to colorectal cancer.

Monday, October 21, 2024, 4:45 PM ET

Colorectal cancer is a prevalent disease with estimated 1.93 million new cases in 2020. Researchers at Nazarbayev University and Al-Farabi Kazakh National University used PLGA-PEG-COOH (AI078) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop CASIN loaded nanoparticles for targeted therapy of colorectal cancer. This research holds promise to provide for treatment of cancer. Read more: Kadyr, Sanazar, Altyn Zhuraliyeva, Aislu Yermekova, Aigerim Makhambetova, Daulet B. Kaldybekov, Ellina A. Mun, Denis Bulanin, Sholpan N. Askarova, and Bauyrzhan A. Umbayev. "PLGA-PEG Nanoparticles Loaded with Cdc42 Inhibitor for Colorectal Cancer Targeted Therapy." Pharmaceutics 16, no. 10 (2024): 1301. https://www.mdpi.com/1999-4923/16/10/1301

“Abstract: Background/Objectives: An inhibitor of small Rho GTPase Cdc42, CASIN, has been shown to reduce cancer cell proliferation, migration, and invasion, yet it has several limitations, including rapid drug elimination and low bioavailability, which prevents its systemic administration. In this study, we designed and characterized a nanoparticle-based delivery system for CASIN encapsulated within poly(lactide-co-glycolide)-block-poly(ethylene glycol)-carboxylic acid endcap nanoparticles (PLGA-PEG-COOH NPs) for targeted inhibition of Cdc42 activity in colon cancer. Methods: We applied DLS, TEM, and UV–vis spectroscopy methods to characterize the size, polydispersity index, zeta potential, encapsulation efficiency, loading capacity, and in vitro drug release of the synthesized nanoparticles. The CCK-8 cell viability test was used to study colorectal cancer cell growth in vitro. Results: We showed that CASIN-PLGA-PEG-COOH NPs were smooth, spherical, and had a particle size of 86 ± 1 nm, with an encapsulation efficiency of 66 ± 5% and a drug-loading capacity of 5 ± 1%. CASIN was gradually released from NPs, reaching its peak after 24 h, and could effectively inhibit the proliferation of HT-29 (IC50 = 19.55 µM), SW620 (IC50 = 9.33 µM), and HCT116 (IC50 = 10.45 µM) cells in concentrations ranging between 0.025–0.375 mg/mL. CASIN-PLGA-PEG-COOH NPs demonstrated low hemolytic activity with a hemolytic ratio of less than 1% for all tested concentrations. Conclusion: CASIN-PLGA-PEG-COOH NPs have high encapsulation efficiency, sustained drug release, good hemocompatibility, and antitumor activity in vitro. Our results suggest that PLGA-PEG-COOH nanoparticles loaded with CASIN show potential as a targeted treatment for colorectal cancer and could be recommended for further in vivo evaluation. Keywords: Cdc42; CASIN; colorectal cancer; PLGA-PEG-COOH; nanoparticles”

PLGA-PEG-COOH (Cat# AI078): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AI078#h

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PCL from PolySciTech used in development of nano-polyhedron drug delivery platform.

Monday, October 14, 2024, 4:22 PM ET

Combinations of metal compounds with polymers can enable unique drug-delivery options. Researchers at China Three Gorges University used PCL (AP257) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create mixed nanoparticles containing selenium and Riboflavin as a model drug delivery system. This research holds promise to provide for a wide array of targeted delivery applications. Read more: Zhu, Lixian, Yanhua Wang, Luping Rao, and Xin Yu. "Se-incorporated polycaprolactone spherical polyhedron enhanced vitamin B2 loading and prolonged release for potential application in proliferative skin disorders." Colloids and Surfaces B: Biointerfaces 245 (2025): 114295. https://www.sciencedirect.com/science/article/pii/S092777652400554X

“Highlights: The introduction of Se into PCL@VitB2 spherical polyhedrons reduces their particle size and crystallinity. Se-PCL spherical polyhedrons perform higher loading efficiency for Vitamin B2 than pure PCL spherical polyhedrons. Se-PCL@VitB2 spherical polyhedrons exhibit slowly prolonged Vitamin B2 release in physical buffers. Se-PCL@VitB2 spherical polyhedrons present strong inhibitory effect on the growth of epidermal HaCat cells, but are compatible to BMSC cells. Abstract: Development of novel drug vehicles for vitamin B2 (VitB2) delivery is very important for designing controllable release system to improve epidermal growth and bone metabolism. In this work, selenium (Se)-incorporated polycaprolactone (PCL) spherical polyhedrons are successfully synthesized via a single emulsion solvent evaporation method which is utilized to load VitB2 to fabricate cell-responsive Se-PCL@VitB2 delivery systems. Their physicochemical properties are characterized by DLS, SEM, XRD, FTIR, and TGA-DSC. The release kinetics of VitB2 or Se from the samples are investigated in PBS solution (pH = 2.0, 5.0, 7.4, 8.0 and 12.0). The cytocompatibilities are also evaluated with normal BMSC and epidermal HaCat cells. Results exhibit that Se-PCL@VitB2 particles presents spherical polyhedral morphology (approximately (3.25 ± 0.46) μm), negative surface charge (-(54.03 ± 2.94) mV), reduced crystallinity and good degradability. Stability experiments imply that both VitB2 and Se might be uniformly dispersed in PCL matrix. And the incorporation of Se facilely promotes the loading of VitB2. The encapsulation efficiency and loading capacity are (98.42 ± 1.06)% and (76.25 ± 1.27) for Se-PCL@VitB2 sample. Importantly, it exhibits more prolonged release of both VitB2 and Se in neutral PBS solution (pH = 7.4) than other pH conditions. Presumably, the electrostatic interaction between Se, VitB2 and PCL contribute to its release mode. Cell experiments show that Se-PCL@VitB2 presents strong cytotoxicity to HaCat cells mainly due to the cytotoxic effect of Se anions and PCL degradation products. However, it exhibits weak inhibitory effect on BMSC cells. These note that the synthesized Se-PCL@VitB2 particles can be promising drug vehicles for potential application in epidermal proliferative disorders.”

PCL (Cat# AP257): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AP257#h

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PLGA-PEG-Maleimide and PEG-PLGA used in development of nanoparticles for oral delivery of semaglutide

Monday, October 14, 2024, 4:21 PM ET

GLP1 agonists are widely used in treatment of diabetes and other disease states. These drugs have poor oral bioavailability. Researchers at Universidade do Porto, Novo Nordisk, KTH Royal Institute of Technology, Roslagstullsbacken, University of Groningen used PLGA-PEG-Mal (AI110) and mPEG-PLGA (AK106) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles to pass through the intestine to provide for oral delivery of semaglutide. This research holds promise to provide for improved treatment of diabetes. Read more: Pinto, Soraia, Juliana Viegas, Cecília Cristelo, Catarina Pacheco, Sofia Barros, Stephen T. Buckley, Javad Garousi, Torbjörn Gräslund, Hélder A. Santos, and Bruno Sarmento. "Bioengineered Nanomedicines Targeting the Intestinal Fc Receptor Achieve the Improved Glucoregulatory Effect of Semaglutide in a Type 2 Diabetic Mice Model." ACS nano (2024). https://pubs.acs.org/doi/abs/10.1021/acsnano.4c11172

“The oral administration of the glucagon-like peptide-1 analogue, semaglutide, remains a hurdle due to its limited bioavailability. Herein, neonatal Fc receptor (FcRn)-targeted nanoparticles (NPs) were designed to enhance the oral delivery of semaglutide. The nanocarriers were covalently linked to the FcRn-binding peptide FcBP or the affibody molecule ZFcRn that specifically binds to the human FcRn (hFcRn) in a pH-dependent manner. These FcRn-targeted ligands were selected over the endogenous ligands of the receptor (albumin and IgG) due to their smaller size and simpler structure, which could facilitate the transport of functionalized NPs through the tissues. The capacity of FcRn-targeted semaglutide-NPs in controlling the blood glucose levels was evaluated in an hFcRn transgenic mice model, where type 2 diabetes mellitus (T2DM) was induced via intraperitoneal injection of nicotinamide followed by streptozotocin. The encapsulation of semaglutide into FcRn-targeted NPs was translated in an improved glucoregulatory effect in T2DM-induced mice when compared to the oral free semaglutide or nontargeted NP groups, after daily oral administrations for 7 days. Notably, a similar glucose-lowering response was observed between both FcRn-targeted NPs and the subcutaneous semaglutide groups. An increase in insulin pancreatic content and a recovery in β cell mass were visualized in the mice treated with FcRn-targeted semaglutide-NPs. The biodistribution of fluorescently labeled NPs through the gastrointestinal tract demonstrated that the nanosystems targeting the hFcRn are retained longer in the ileum and colorectum, where the expression of FcRn is more prevalent, than nontargeted NPs. Therefore, FcRn-targeted nanocarriers proved to be an effective platform for improving the pharmacological effect of semaglutide in a T2DM-induced mice model.”

PEG-PLGA (Cat# AK106): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AK106#h

PLGA-PEG-Mal (Cat# AI110): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AI110#h

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PLGA-PEG-amine from PolySciTech used in development of nanoparticles for brain-tissue penetration

Monday, September 30, 2024, 2:11 PM ET

Delivery of medicinal molecules into the brain is difficult due to the blood-brain-barrier. Researchers at University of Technology Sydney and The University of Adelaide used PLGA-PEG-NH2 (AI058) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles enveloped in a protein corona. They used these particles to investigate mechanisms of uptake and delivery in brain tissue. This research holds promise to provide for improved therapies against brain diseases such as cancer and Alzheimer’s. Read more: Morshed, Nabila, Claire Rennie, Wei Deng, Lyndsey Collins-Praino, and Andrew Care. "Serum-derived protein coronas affect nanoparticle interactions with brain cells." Nanotechnology 35, no. 49 (2024): 495101. https://new.iopscience.iop.org/article/10.1088/1361-6528/ad7b40

“Neuronanomedicine is an emerging field bridging the gap between neuromedicine and novel nanotherapeutics. Despite promise, clinical translation of neuronanomedicine remains elusive, possibly due to a dearth of information regarding the effect of the protein corona on these neuronanomedicines. The protein corona, a layer of proteins adsorbed to nanoparticles following exposure to biological fluids, ultimately determines the fate of nanoparticles in biological systems, dictating nanoparticle–cell interactions. To date, few studies have investigated the effect of the protein corona on interactions with brain-derived cells, an important consideration for the development of neuronanomedicines. Here, two polymeric nanoparticles, poly(lactic-co-glycolic acid) (PLGA) and PLGA-polyethylene glycol (PLGA-PEG), were used to obtain serum-derived protein coronas. Protein corona characterization and liquid chromatography mass spectrometry analysis revealed distinct differences in biophysical properties and protein composition. PLGA protein coronas contained high abundance of globins (60%) and apolipoproteins (21%), while PLGA-PEG protein coronas contained fewer globins (42%) and high abundance of protease inhibitors (28%). Corona coated PLGA nanoparticles were readily internalized into microglia and neuronal cells, but not into astrocytes. Internalization of nanoparticles was associated with pro-inflammatory cytokine release and decreased neuronal cell viability, however, viability was rescued in cells treated with corona coated nanoparticles. These results showcase the importance of the protein corona in mediating nanoparticle–cell interactions.”

PLGA-PEG-Mal (Cat# AI058): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AI058#h

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Video link: https://youtu.be/d3Z4GLgzcss

Network Upgrade Outage

Thursday, September 19, 2024, 10:20 AM ET

Notice: Akina, Inc. orders placed after 12:00 pm EST, Thursday, September 19th and Friday, September 20th, 2024 may experience delay as we migrate to a new internal server. We expect to resume fulfillment no later than Monday morning, September 23rd, 2024.

PLGA from PolySciTech used in development of nanoparticles for treatment of atherosclerosis

Tuesday, September 17, 2024, 4:53 PM ET

Atherosclerosis (heart-disease) is due to formation of lipid-laden plaques in the arteries. These plaques typically express immunosuppressive signals which prevents their removal by immune system. Recently, researchers at University of Ottawa utilized PLGA (AP023) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles to deliver immunotargeting compounds to plaques. This research holds promise as a potential treatment for heart disease. Read more: Patel, Yukta, Shireesha Manturthi, Saras Tiwari, Esha Gahunia, Amandine Courtemanche, Michelle Gandelman, Marceline Côté, and Suresh Gadde. "Development of Pro-resolving and Pro-efferocytic Nanoparticles for Atherosclerosis Therapy." ACS Pharmacology & Translational Science (2024). https://pubs.acs.org/doi/abs/10.1021/acsptsci.4c00292

“Atherosclerosis is a major contributor to cardiovascular diseases with a high global prevalence. It is characterized by the formation of lipid-laden plaques in the arteries, which eventually lead to plaque rupture and thrombosis. While the current lipid-lowering therapies are generally effective in lowering the risk of cardiovascular events, they do not address the underlying causes of disease. Defective resolution of inflammation and impaired efferocytosis are the main driving forces of atherosclerosis. Macrophages recognize cells for clearance by the expression of “eat me” and “do not eat me” signals, including the CD47-SIRPα axis. However, the “do not eat me” signal CD47 is overexpressed in atherosclerotic plaques, leading to compromised efferocytosis and secondary necrosis. In this context, prophagocytic antibodies have been explored to stimulate the clearance of apoptotic cells, but they are nonspecific and impact healthy tissues. In macrophages, downstream of signal regulatory protein α, lie protein tyrosine phosphatases, SHP 1/2, which can serve as effective targets for selectively phagocytosing apoptotic cells. While increasing the efferocytosis targets the end stages of lesion development, the underlying issue of inflammation still persists. Simultaneously increasing efferocytosis and reducing inflammation can be effective therapeutic strategies for managing atherosclerosis. For instance, IL-10 is a key anti-inflammatory mediator that enhances efferocytosis via phosphoSTAT3 (pSTAT3) activation. In this study, we developed a combination nanotherapy by encapsulating an SHP-1 inhibitor (NSC 87877) and IL-10 in a single nanoparticle platform [(S + IL)-NPs] to enhance efferocytosis and inflammation resolution. Our studies suggest that (S + IL)-NPs successfully encapsulated both agents, entered the macrophages, and delivered the agents into intracellular compartments. Additionally, (S + IL)-NPs decreased inflammation by suppressing pro-inflammatory markers and enhancing anti-inflammatory mediators. They also exhibited the potential for improved phagocytic activity via pSTAT3 activation. Our nanomedicine-mediated upregulation of the anti-inflammatory and efferocytic responses in macrophages shows promise for the treatment of atherosclerosis.”

PLGA-PEG-Mal (Cat# AP023): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AP023#h

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PLGA-PEG-Mal from PolySciTech used in development of nano-delivery system for glioblastoma treatment

Tuesday, September 17, 2024, 4:53 PM ET

Glioblastoma is an aggressive brain cancer that is difficult to treat. Researchers at Southern University of Science and Technology, University of Texas Southwestern Medical Center, Xuzhou Medical University used PLGA-PEG-Maleimide (AI110) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles for targeting glioblastoma. They utilized this as part of a multifunctional system to maximize both radiotherapy and also immunotherapy against glioblastoma. Read more: Wen, Xin, Zhiying Shao, Xueting Chen, Hongmei Liu, Hui Qiu, Xin Ding, Debao Qu, Hui Wang, Andrew Z. Wang, and Longzhen Zhang. "A multifunctional targeted nano-delivery system with radiosensitization and immune activation in glioblastoma." Radiation Oncology 19, no. 1 (2024): 1-20. https://ro-journal.biomedcentral.com/articles/10.1186/s13014-024-02511-9

“Glioblastoma (GBM), the most common primary brain malignancy in adults, is notoriously difficult to treat due to several factors: tendency to be radiation resistant, the presence of the blood brain barrier (BBB) which limits drug delivery and immune-privileged status which hampers effective immune responses. Traditionally, high-dose irradiation (8 Gy) is known to effectively enhance anti-tumor immune responses, but its application is limited by the risk of severe brain damage. Currently, conventional dose segmentation (2 Gy) is the standard radiotherapy method, which does not fully exploit the potential of high-dose irradiation for immune activation. The hypothesis of our study posits that instead of directly applying high doses of radiation, which is risky, a strategy could be developed to harness the immune-stimulating benefits of high-dose irradiation indirectly. This involves using nanoparticles to enhance antigen presentation and immune responses in a safer manner. Angiopep-2 (A2) was proved a satisfactory BBB and brain targeting and Dbait is a small molecule that hijack DNA double strand break damage (DSB) repair proteins to make cancer cells more sensitive to radiation. In view of that, the following two nanoparticles were designed to combine immunity of GBM, radiation resistance and BBB innovatively. One is cationic liposome nanoparticle interacting with Dbait (A2-CL/Dbait NPs) for radiosensitization effect; the other is PLGA-PEG-Mal nanoparticle conjugated with OX40 antibody (A2-PLGA-PEG-Mal/anti-OX40 NPs) for tumor-derived protein antigens capture and optimistic immunoregulatory effect of anti-OX40 (which is known to enhance the activation and proliferation T cells). Both types of nanoparticles showed favorable targeting and low toxicity in experimental models. Specifically, the combination of A2-CL/Dbait NPs and A2-PLGA-PEG-Mal/anti-OX40 NPs led to a significant extension in the survival time and a significant tumor shrinkage of mice with GBM. The study demonstrates that combining these innovative nanoparticles with conventional radiotherapy can effectively address key challenges in GBM treatment. It represents a significant step toward more effective and safer therapeutic options for GBM patients.”

PLGA-PEG-Mal (Cat# AI110): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AI110#h

NEW: Corbion Purasorb® Polymers: https://akinainc.com/polyscitech/products/purasorb/

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Video: https://youtu.be/jLCzFHNPN2c

PLGA-PEG-PLGA Thermogels from PolySciTech used in development of controlled antibody release system

Tuesday, September 17, 2024, 4:52 PM ET

Thermogels have the ability to dissolve in cold water and form solid, gel structures when heated to body temperature. This allows them to deliver delicate molecules, like antibodies, which typically break down under normal processing conditions to form microparticles. Researchers at the Polish Academy of Sciences used PLGA-PEG-PLGA (AK012, AK024, AK088, AK091) and PLCL-PEG-PLCL (AK108) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create a gel to deliver antibodies. This research holds promise to provide for improved biotherapy techniques in the future. Read more: Lipowska-Kur, Daria, Łukasz Otulakowski, Urszula Szeluga, Katarzyna Jelonek, and Alicja Utrata-Wesołek. "Diverse Strategies to Develop Poly (ethylene glycol)–Polyester Thermogels for Modulating the Release of Antibodies." Materials 17, no. 18 (2024): 4472. https://www.mdpi.com/1996-1944/17/18/4472

“Abstract: In this work, we present basic research on developing thermogel carriers containing high amounts of model antibody immunoglobulin G (IgG) with potential use as injectable molecules. The quantities of IgG loaded into the gel were varied to evaluate the possibility of tuning the dose release. The gel materials were based on blends of thermoresponsive and degradable ABA-type block copolymers composed of poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA–PEG–PLGA) or poly(lactide-co-caprolactone)-b-poly(ethylene glycol)-b-(lactide-co-caprolactone) (PLCL–PEG–PLCL). Primarily, the gels with various amounts of IgG were obtained via thermogelation, where the only factor inducing gel formation was the change in temperature. Next, to control the gels’ mechanical properties, degradation rate, and the extent of antibody release, we have tested two approaches. The first one involved the synergistic physical and chemical crosslinking of the copolymers. To achieve this, the hydroxyl groups located at the ends of the PLGA–PEG–PLGA chain were modified into acrylate groups. In this case, the thermogelation was accompanied by chemical crosslinking through the Michael addition reaction. Such an approach increased the dynamic mechanical properties of the gels and simultaneously prolonged their decomposition time. An alternative solution was to suspend crosslinked PEG–polyester nanoparticles loaded with IgG in a PLGA–PEG–PLGA gelling copolymer. We observed that loading IgG into thermogels lowered the gelation temperature (TGEL) value and increased the storage modulus of the gels, as compared with gels without IgG. The prepared gel materials were able to release the IgG from 8 up to 80 days, depending on the gel formulation and on the amount of loaded IgG. The results revealed that additional, chemical crosslinking of the thermogels and also suspension of particles in the polymer matrix substantially extended the duration of IgG release. With proper matching of the gel composition, environmental conditions, and the type and amount of active substances, antibody-containing thermogels can serve as effective IgG delivery materials. Keywords: thermogels; sol-gel transition; tandem gelation; polymer degradation; nanoparticles; antibody”

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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.”

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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.”

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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.”

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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.”

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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.”

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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”

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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.”

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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.”

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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.”

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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.”

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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”

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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.”

PLGA-PEG-PLGA AK097: https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AK097#h

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These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.22652912139893 seconds)