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

 

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.”

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Video: https://youtu.be/h2JEHB5Uvz0

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

 

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

 

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.

 

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.

 

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.

 

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

 

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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