PLGA-PEG-PLGA nanogel system used in development of brain cancer treatment.

 

Glioblastoma is a common form of brain cancer which is difficult to treat. One way to bypass the blood-brain-barrier to deliver therapeutics to the site is to implant a nanogel system into the cranial cavity directly. Researchers at Johns Hopkins University, St. John’s University, and OncoGone, Inc. used PLGA-PEG-PLGA ( cat# AK012, AK019) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop a pellet system for controlled delivery of Temozolomide and paclitaxel to brain tumors. This research holds promise to improve cancer therapy in the future. Read more: Slika, Hasan, Aanya Shahani, Kranthi Gattu, Varsha Mundrathi, Ameilia A. Solan, Brianna Gonzalez, Tasmima N. Haque et al. "Intracranial Nanogel Pellets Carrying Temozolomide and Paclitaxel for Adjuvant Brain Cancer Therapy." Molecular Pharmaceutics (2024). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.4c00708

“Glioblastoma multiforme is the most frequently diagnosed primary malignant brain tumor. Despite multimodal therapy with surgical resection, radiation therapy, and chemotherapy, recurrence of the tumor is almost always guaranteed due to the infiltrative nature of the disease. Moreover, the blood brain barrier imparts an additional layer of complexity by impeding the delivery of therapeutic agents to the tumor, hence limiting the efficacy of systemically delivered drugs. Hence, to overcome this obstacle and avoid treatment resistance, the local delivery of combination therapies has risen as an appealing adjuvant treatment. The present study describes the creation of a novel PLGA–PEG-PLGA-based nanogel pellet system for the interstitial delivery of Temozolomide (TMZ) and paclitaxel (PTX) to the brain. The nanogel pellet was shown to be stable as a pellet at ambient temperature, absorb water, change to a gel formulation at physiological temperature, and achieve gradual long-term release of TMZ and PTX in vitro. Additionally, in vivo testing of the TMZ/PTX-loaded nanogel pellets in an orthotopic CT2A mouse model and an orthotopic 9L rat model has shown an acceptable safety profile when implanted intracranially and a significant improvement in overall survival.”

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Fluorescent PLGA from PolySciTech used in development of carrier system for cell immunotherapy as treatment of infection.

 

Although periodontitis is an oral infection affecting teeth, it has been strongly associated with diseases of significantly higher morbidity and mortality such as cardiovascular disease, diabetes, and rheumatoid arthritis. Macrophages (immune cells) can be directed to control immune response as well as healing and other biological processes by attaching cellular backpacks to them. Researchers at Harvard University, Massachusetts Institute of Technology, and Niigata University used PLGA-rhodamine and PLGA-CY5 (AV011, AV034) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop particles which can control macrophage behavior. This research holds promise to treat a wide range of disease states. Read more: Nakajima, Mayuka, Neha Kapate, John R. Clegg, Mayumi Ikeda-Imafuku, Kyung Soo Park, Ninad Kumbhojkar, Vinny Chandran Suja et al. "Backpack-carrying macrophage immunotherapy for periodontitis." Journal of Controlled Release 377 (2025): 315-323. https://www.sciencedirect.com/science/article/pii/S016836592400782X

“Highlights: M2 macrophages can suppress inflammation in periodontitis. IL-4 loaded cellular backpacks (BPs) were engineered for maintaining macrophages in M2 phenotype. M2 cells carrying IL-4 BPs (BP-M2 cells) were injected into the inflamed gingiva. M2 cells remained in the injected tissue and their therapeutic efficacy was observed. BP-M2 cells offer a promising local therapy for treating periodontitis. Abstract: Cell immunotherapy is a promising therapeutic modality to combat unmet medical needs. Macrophages offer a prominent cell therapy modality since their phenotypic plasticity allows them to perform a variety of roles including defending against pathogens, inducing/suppressing adaptive immunity, and aiding in wound healing. At the same time, this plasticity is a major hurdle in implementation of macrophage therapy. This hurdle can be overcome by cellular backpacks (BPs), discoidal particles that adhere on the macrophage surface and regulate M1/M2 phenotypic shift in an environment-independent manner. In this study, we engineered IL-4 BPs for maintaining macrophages in the M2 phenotype to regulate excess inflammation in periodontitis, a major oral infectious disease. IL-4 BPs induced and maintained M2 phenotype in macrophages in vitro for several days. After injection of macrophages carrying IL-4 BPs into the gingiva, the cells stayed in the tissue for over 5 days and maintained the M2 phenotype in the disease sites. Furthermore, treatment with IL-4 BP-macrophages significantly suppressed the disease progression. Altogether, a treatment with BP-carrying macrophages offers a promising local therapy against periodontitis.”

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mPEG-PLGA from PolySciTech used in development of advanced radiotherapy of brain cancer

 

Glioblastoma is a form of brain cancer which has high mortality and limited treatment options. Currently only surgery and radiotherapy are available as treatments. Radiotherapy can be enhanced by delivery of radiosensitizers to the glioblastoma region. Researchers at Fuzhou University, Fujian Medical University School, and Fujian Agriculture and Forestry University utilized mPEG-PLGA (AK037) to delivery hemin to glioblastoma to improve the efficacy of radiotherapy. This research holds promise to improve therapy of brain tumors in the future. Read more: Yang, Bo, Xiaohang Jiang, Yifan Liu, Guangwei Zheng, Yanjuan Li, Fuli Xin, and Feng Lu. "Erythrocyte Membrane-Camouflaged Hemin-Based Nanoplatform for Radiotherapy of Glioblastoma." ACS Applied Nano Materials (2024). https://pubs.acs.org/doi/abs/10.1021/acsanm.4c04992

“Glioblastoma, accounting for 44% of all malignant brain tumors, is characterized by a dismal prognosis due to high mortality, recurrence, and limited survival time. Current standard treatment, radiotherapy, is resistant to the tumor hypoxic microenvironment, which reduces the effect of radiotherapy. Here, we present a nanoplatform, PLGA-Hemin@RBCM (PHR), which leverages the catalase mimetic activity of hemin to convert tumor-elevated H2O2 into oxygen and hydroxyl radicals, improving tumor oxygenation and enhancing radiotherapy sensitivity. The PEG-PLGA nanomicelle delivery platform improves the biocompatibility and stability of the drug and delays the release of the drug. Camouflaging the nanoparticles with red blood cell membranes not only avoids immune clearance but also prolongs circulation time and enhances tumor accumulation via the EPR effect. In vitro and in vivo studies demonstrate the efficacy of our nanoplatform, offering a promising therapeutic strategy for glioblastoma management in the clinic.”

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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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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.”

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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.”

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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.”

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