Technical Blog
John GarnerJohn 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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PEG-PLGA from PolySciTech used in the development of nanoparticles to deliver anti-tumor agents RG7388 and entinostat for cancer therapy

Thursday, February 22, 2024, 10:18 AM ET

In cancer therapy applications it is possible for specific drugs to work in concert creating a stronger effect than either of them would have on their own. Due to their interactions on several biological pathways, there is good indication that recently discovered RG7388 compound can work with entinostat to treat cancer. Researchers at Queen’s University Belfast and Al-Ahliyya Amman University used PEG-PLGA (Cat# AK010) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create and test the efficacy of nanoparticles loaded with both drugs. This research holds promise to improve cancer therapy in the future. Read more: Abed, Anas, Michelle K. Greene, Alhareth A. Alsa’d, Andrea Lees, Andrew Hindley, Daniel B. Longley, Simon S. McDade, and Christopher J. Scott. "Nanoencapsulation of MDM2 Inhibitor RG7388 and Class-I HDAC Inhibitor Entinostat Enhances their Therapeutic Potential Through Synergistic Antitumor Effects and Reduction of Systemic Toxicity." Molecular Pharmaceutics (2024). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.3c00926

“Inhibitors of the p53–MDM2 interaction such as RG7388 have been developed to exploit latent tumor suppressive properties in p53 in 50% of tumors in which p53 is wild-type. However, these agents for the most part activate cell cycle arrest rather than death, and high doses in patients elicit on-target dose-limiting neutropenia. Recent work from our group indicates that combination of p53–MDM2 inhibitors with the class-I HDAC inhibitor Entinostat (which itself has dose-limiting toxicity issues) has the potential to significantly augment cell death in p53 wild-type colorectal cancer cells. We investigated whether coencapsulation of RG7388 and Entinostat within polymeric nanoparticles (NPs) could overcome efficacy and toxicity limitations of this drug combination. Combinations of RG7388 and Entinostat across a range of different molar ratios resulted in synergistic increases in cell death when delivered in both free drug and nanoencapsulated formats in all colorectal cell lines tested. Importantly, we also explored the in vivo impact of the drug combination on murine blood leukocytes, showing that the leukopenia induced by the free drugs could be significantly mitigated by nanoencapsulation. Taken together, this study demonstrates that formulating these agents within a single nanoparticle delivery platform may provide clinical utility beyond use as nonencapsulated agents. KEYWORDS:cancer nanoparticles Entinostat nutlin toxicity combination therapy”

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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a free scientific/networking conference hosted by Akina (http://bprconference.com/).

PLGA-PEG-Dibenzocyclooctyne from PolySciTech used in research on PARPi treatment for ovarian cancer.

Friday, February 16, 2024, 4:21 PM ET

On average, about 12,740 women die from ovarian cancer each year in USA (American Cancer Society).Researchers at University of Maryland used PLGA-PEG-COOH (AI171) and PLGA-PEG-DBCO (AI205) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles loaded with talazoparib as a strategy to treat chemotherapy resistant ovarian cancer. This research holds promise to improve cancer therapy in the future. Read more: Sorrin, Aaron, Anika Dasgupta, Kathryn McNaughton, Carla Arnau Del Valle, Keri Zhou, Cindy Liu, Dana M. Roque, and Huang Chiao Huang. "Co-Packaged PARP inhibitor and photosensitizer for targeted photo-chemotherapy of 3D ovarian cancer spheroids." Cell & Bioscience 14, no. 1 (2024): 1-13. https://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-024-01197-6

“Background: Within the last decade, poly(ADP-ribose) polymerase inhibitors (PARPi) have emerged in the clinic as an effective treatment for numerous malignancies. Preclinical data have demonstrated powerful combination effects of PARPi paired with photodynamic therapy (PDT), which involves light-activation of specialized dyes (photosensitizers) to stimulate cancer cell death through reactive oxygen species generation. Results: In this report, the most potent clinical PARP inhibitor, talazoparib, is loaded into the core of a polymeric nanoparticle (NP-Tal), which is interfaced with antibody-photosensitizer conjugates (photoimmunoconjugates, PICs) to form PIC-NP-Tal. In parallel, a new 3D fluorescent coculture model is developed using the parental OVCAR-8-DsRed2 and the chemo-resistant subline, NCI/ADR-RES-EGFP. This model enables quantification of trends in the evolutionary dynamics of acquired chemoresistance in response to various treatment regimes. Results reveal that at a low dosage (0.01 μM), NP-Tal kills the parental cells while sparing the chemo-resistant subline, thereby driving chemoresistance. Next, PIC-NP-Tal and relevant controls are evaluated in the 3D coculture model at multiple irradiation doses to characterize effects on total spheroid ablation and relative changes in parental and subline cell population dynamics. Total spheroid ablation data shows potent combination effects when PIC and NP-Tal are co-administered, but decreased efficacy with the conjugated formulation (PIC-NP-Tal). Analysis of cell population dynamics reveals that PIC, BPD + NP-Tal, PIC + NP-Tal, and PIC-NP-Tal demonstrate selection pressures towards chemoresistance. Conclusions: This study provides key insights into manufacturing parameters for PARPi-loaded nanoparticles, as well as the potential role of PDT-based combination therapies in the context of acquired drug resistance.”

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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a​ free ​scientific/​networking conference hosted by Akina (http://bprconference.com/​).

PLGA-Rhodamine from PolySciTech used in research on cancer-targeting nanoparticles

Friday, February 16, 2024, 4:20 PM ET

Paclitaxel is a chemotherapeutic agent which prevents cellular growth. Due to its non-specific nature, it damages both healthy and cancerous cells which leads to significant side-effects. Researchers at Purdue University used PLGA-rhodamine (AV011) from PolySciTech Division of Akina, Inc (www.polyscitech.com) to develop ATP targeted nanoparticles for localization of PTX at a cancer site and to recruit immune cells to the cancer. This research holds promise to improve cancer therapy in the future. Read more: Kwon, Soonbum, Fanfei Meng, Hassan Tamam, Hytham H. Gadalla, Jianping Wang, Boyang Dong, Amber S. Hopf Jannasch, Timothy L. Ratliff, and Yoon Yeo. "Systemic Delivery of Paclitaxel by Find-Me Nanoparticles Activates Antitumor Immunity and Eliminates Tumors." ACS nano (2024). https://pubs.acs.org/doi/abs/10.1021/acsnano.3c11445

“Local delivery of immune-activating agents has shown promise in overcoming an immunosuppressive tumor microenvironment (TME) and stimulating antitumor immune responses in tumors. However, systemic therapy is ultimately needed to treat tumors that are not readily locatable or accessible. To enable systemic delivery of immune-activating agents, we employ poly(lactic-co-glycolide) (PLGA) nanoparticles (NPs) with a track record in systemic application. The surface of PLGA NPs is decorated with adenosine triphosphate (ATP), a damage-associated molecular pattern to recruit antigen-presenting cells (APCs). The ATP-conjugated PLGA NPs (NPpD-ATP) are loaded with paclitaxel (PTX), a chemotherapeutic agent inducing immunogenic cell death to generate tumor antigens in situ. We show that the NPpD-ATP retains ATP activity in hostile TME and provides a stable “find-me” signal to recruit APCs. Therefore, the PTX-loaded NPpD-ATP helps populate antitumor immune cells in TME and attenuate the growth of CT26 and B16F10 tumors better than a mixture of PTX-loaded NPpD and ATP. Combined with anti-PD-1 antibody, PTX-loaded NPpD-ATP achieves complete regression of CT26 tumors followed by antitumor immune memory. This study demonstrates the feasibility of systemic immunotherapy using a PLGA NP formulation that delivers ICD-inducing chemotherapy and an immunostimulatory signal. chemoimmunotherapy systemic delivery PLGA nanoparticles adenosine triphosphate immunogenic cell death paclitaxel”

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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a​ free ​scientific/​networking conference hosted by Akina (http://bprconference.com/​).

PLGA from PolySciTech used in development of oral delivery system for liraglutide

Friday, February 16, 2024, 4:19 PM ET

Liraglutide is a GLP-1 analog which provides for treatment of diabetes. Due to it’s low bioavailability, it can not be normally administered orally. Recently, researchers at Yantai University utilized PLGA (AP040) from PolySciTech Division of Akina, Inc (www.polyscitech.com) to develop oral delivery nanoparticles for liraglutide treatment of diabetes. This research holds promise to treat this chronic disease. Read more: Zhao, Zhenyu, Ruihuan Ding, Yumei Wang, Ranran Yuan, Houqian Zhang, Tianyang Li, Wei Zheng, Entao Chen, Aiping Wang, and Yanan Shi. "Sulfobetaine modification of poly (D, l-lactide-co-glycolic acid) nanoparticles enhances mucus permeability and improves bioavailability of orally delivered liraglutide." Journal of Drug Delivery Science and Technology (2024): 105437. https://www.sciencedirect.com/science/article/pii/S1773224724001059

“The glucagon-like peptide-1 (GLP-1) analogue used to treat diabetes is an increasingly popular polypeptide protein therapeutic, commonly marketed as an injection. However, the effective oral administration of peptide drugs remains challenging because of their extremely low bioavailability. In recent years, a number of delivery systems that have been shown to be effective in improving the therapeutic efficacy of oral drugs. Herein, liraglutide was employed as a model drug and amphoteric sulfobetaine (SB12) was selected for the surface modification of poly (D, L-lactide-co-glycolic acid) (PLGA) nanoparticles (NPs) to obtain hydrophilic and electroneutral SB12-NPs. The functional SB12-NPs were first screened to identify the optimal prescription process and obtained from the final prescription were evaluated. The particle size, zeta potential, encapsulation efficiency (EE%) and drug-loading (DL%) of SB12-NPs were 87.25 ± 0.77 nm, −3.91 ± 1.88 mV, 77.45% ± 1.62%, and 10.46% ± 0.21%, respectively. The cellular uptake of Lira-SB12 NPs was significantly better than that of free liraglutide, and verified that it was transported mainly through endocytosis mediated by clathrin- and lipid raft–mediated. The trans-mucous permeability (2.86-fold) and intestinal permeability (1.79-fold) of SB12-NPs were significantly higher than those of free liraglutide. Single and multiple doses of SB12-NPs showed that the blood sugar level of diabetic mice could be lower to about 70% of the initial value. The SB12-NPs demonstrated a higher relative bioavailability of 9.59% compared with that of oral pure liraglutide (5.13%). Thus, SB12-modified PLGA NPs with hydrophilic and electroneutral surface properties can significantly improve mucus permeability and oral bioavailability, and have the potential to be applied for oral delivery of peptides and proteins.”

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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a​ free ​scientific/​networking conference hosted by Akina (http://bprconference.com/​).

PGACL from PolySciTech used in development of flexible electronics for implantable devices

Tuesday, February 6, 2024, 4:54 PM ET

Transient electronics describe electronic systems which have the ability to dissolve after the intended use. Researchers at Korea University, SK Hynix, Hanwha Systems Co., Ltd., North Carolina State University, Samsung Electronics Co., Ltd, Poly(glycolide-co-caprolactone) (APB004, APB007, APB008) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create a stretchy platform for creating degradable backing for implantable electronics. This technology holds promise to provide for a biological-electrical interface. Read more: Shin, Jeong-Woong, Dong-Je Kim, Tae-Min Jang, Won Bae Han, Joong Hoon Lee, Gwan-Jin Ko, Seung Min Yang et al. "Highly Elastic, Bioresorbable Polymeric Materials for Stretchable, Transient Electronic Systems." Nano-Micro Letters 16, no. 1 (2024): 1-13. https://link.springer.com/article/10.1007/s40820-023-01268-2

“Highlights: The paper introduces a bioresorbable elastomer, poly(glycolide-co-ε-caprolactone) (PGCL), with remarkable mechanical properties, including high elongation-at-break (< 1300%), resilience, and toughness (75 MJ m−3) for soft and transient electronics. Fabrication of conducting polymers with PGCL yields stretchable, conductive composites for transient electronic devices, functioning reliably under external strains. The study demonstrates the feasibility of a disintegrable electronic suture system with on-demand drug delivery for rapid recovery of post-surgical wounds on soft, time-dynamic tissues or versatile biomedical areas of interest. Substrates or encapsulants in soft and stretchable formats are key components for transient, bioresorbable electronic systems; however, elastomeric polymers with desired mechanical and biochemical properties are very limited compared to non-transient counterparts. Here, we introduce a bioresorbable elastomer, poly(glycolide-co-ε-caprolactone) (PGCL), that contains excellent material properties including high elongation-at-break (< 1300%), resilience and toughness, and tunable dissolution behaviors. Exploitation of PGCLs as polymer matrices, in combination with conducing polymers, yields stretchable, conductive composites for degradable interconnects, sensors, and actuators, which can reliably function under external strains. Integration of device components with wireless modules demonstrates elastic, transient electronic suture system with on-demand drug delivery for rapid recovery of post-surgical wounds in soft, time-dynamic tissues. Biodegradable elastomer; Conductive polymer composites; Biomedical device; Transient electronics”

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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a​ free ​scientific/​networking conference hosted by Akina (http://bprconference.com/​).

Fluorescently labelled PLGA from PolySciTech used in development of oral semaglutide delivery system

Wednesday, January 31, 2024, 11:24 AM ET

Diabetes is a widespread disease affecting roughly 38.4 million people of all ages. GLP1 analog semaglutide can be utilized to treat diabetes. Researchers from Universidade do Porto (Portugal), University of Groningen (Netherlands), Novo Nordisk, KTH Royal Institute of Technology, Uppsala University (Sweden), and University of Helsinki (Finland), used fluorescent PLGA-FKR648 (cat# AV015) from PolySciTech Division of Akina, Inc (www.polyscitech.com) to develop oral delivery nanoparticles for semaglutide treatment of diabetes. This research holds promise to improve diabetes treatment. Read more: Pinto, Soraia, Mahya Hosseini, Stephen T. Buckley, Wen Yin, Javad Garousi, Torbjörn Gräslund, Sven van Ijzendoorn, Hélder A. Santos, and Bruno Sarmento. "Nanoparticles targeting the intestinal Fc receptor enhance intestinal cellular trafficking of semaglutide." Journal of Controlled Release 366 (2024): 621-636. https://www.sciencedirect.com/science/article/pii/S0168365924000191

“Highlights: Semaglutide was successfully incorporated into FcRn-targeted polymeric nanoparticles. FcRn-targeted nanoparticles bound to hFcRn in a pH-dependent manner, with a stronger interaction at pH 6 than at pH 7.4. FcRn-targeted nanoparticles showed higher interaction with in vitro intestinal models than non-targeted nanoparticles. Injection of nanomedicines into intestinal organoids' lumen is a promising tool to evaluate cell-nanopartices interaction. Abstract: Semaglutide is the first oral glucagon-like peptide-1 (GLP-1) analog commercially available for the treatment of type 2 diabetes. In this work, semaglutide was incorporated into poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) nanoparticles (NPs) to improve its delivery across the intestinal barrier. The nanocarriers were surface-decorated with either a peptide or an affibody that target the human neonatal Fc receptor (hFcRn), located on the luminal cell surface of the enterocytes. Both ligands were successfully conjugated with the PLGA-PEG via maleimide-thiol chemistry and thereafter, the functionalized polymers were used to produce semaglutide-loaded NPs. Monodisperse NPs with an average size of 170 nm, neutral surface charge and 3% of semaglutide loading were obtained. Both FcRn-targeted NPs exhibited improved interaction and association with Caco-2 cells (cells that endogenously express the hFcRn), compared to non-targeted NPs. Additionally, the uptake of FcRn-targeted NPs was also observed to occur in human intestinal organoids (HIOs) expressing hFcRn through microinjection into the lumen of HIOs, resulting in potential increase of semaglutide permeability for both ligand-functionalized nanocarriers. Herein, our study demonstrates valuable data and insights that the FcRn-targeted NPs has the capacity to promote intestinal absorption of therapeutic peptides.”

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Video: https://youtu.be/wpexfgqfnL0

mPEG-PLGA from PolySciTech used in development of brusatol/docetaxel nanoparticles for prostate cancer treatment

Wednesday, January 31, 2024, 11:23 AM ET

Prostate cancer is the second leading cause of cancer death in American men and 12.9% of men will be diagnosed with this disease during their lifetime. Researchers at Howard University used mPEG-PLGA (cat# AK029) from PolySciTech Division of Akina, Inc (www.polyscitech.com) to make nanoparticles loaded with brusatol and docetaxel. This research holds promise to improve prostate cancer treatment in the future. Read more: Adekiya, Tayo Alex, Madison Moore, Michael Thomas, Gabriel Lake, Tamaro Hudson, and Simeon K. Adesina. "Preparation, Optimization, and In-Vitro Evaluation of Brusatol-and Docetaxel-Loaded Nanoparticles for the Treatment of Prostate Cancer." Pharmaceutics 16, no. 1 (2024): 114. https://www.mdpi.com/1999-4923/16/1/114

“Abstract: Challenges to docetaxel use in prostate cancer treatment include several resistance mechanisms as well as toxicity. To overcome these challenges and to improve the therapeutic efficacy in heterogeneous prostate cancer, the use of multiple agents that can destroy different subpopulations of the tumor is required. Brusatol, a multitarget inhibitor, has been shown to exhibit potent anticancer activity and play an important role in drug response and chemoresistance. Thus, the combination of brusatol and docetaxel in a nanoparticle platform for the treatment of prostate cancer is expected to produce synergistic effects. In this study, we reported the development of polymeric nanoparticles for the delivery of brusatol and docetaxel in the treatment of prostate cancer. The one-factor-at-a-time method was used to screen for formulation and process variables that impacted particle size. Subsequently, factors that had modifiable effects on particle size were evaluated using a 24 full factorial statistical experimental design followed by the optimization of drug loading. The optimization of blank nanoparticles gave a formulation with a mean size of 169.1 nm ± 4.8 nm, in agreement with the predicted size of 168.333 nm. Transmission electron microscopy showed smooth spherical nanoparticles. The drug release profile showed that the encapsulated drugs were released over 24 h. Combination index data showed a synergistic interaction between the drugs. Cell cycle analysis and the evaluation of caspase activity showed differences in PC-3 and LNCaP prostate cancer cell responses to the agents. Additionally, immunoblots showed differences in survivin expression in LNCaP cells after treatment with the different agents and formulations for 24 h and 72 h. Therefore, the nanoparticles are potentially suitable for the treatment of advanced prostate cancer. keywords: prostate cancer; docetaxel; brusatol; nanoparticles; cell cycle; caspase activity; surviving.”

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Video: https://youtu.be/SCy96Ils4PQ

PLGA from PolySciTech used in development of cell membrane-derived nanoparticle for cancer immunotherapy

Thursday, January 18, 2024, 4:53 PM ET

The human immune system is extremely powerful though most forms of cancer have developed ways to evade it. Researchers at University of Texas at Arlington and Southwestern Medical Center Used PLGA (Cat# AP082) from PolySciTech Division of Akina, Inc (www.polyscitech.com) to create particles with HER2 specific coating. These particles localized in tumor areas and delivered cisplatin. This research holds promise to improve therapy against cancer in the future. Read more: Yaman, Serkan, Harish Ramachandramoorthy, Priyanka Iyer, Uday Chintapula, Tam Nguyen, Manoj Sabnani, Tanviben Kotadia et al. "Targeted chemotherapy via HER2-based chimeric antigen receptor (CAR) engineered T-cell membrane coated polymeric nanoparticles." Bioactive Materials 34 (2024): 422-435. https://www.sciencedirect.com/science/article/pii/S2452199X23004309

“Highlights: Membrane coating aids camouflage Nanoparticle delivery. CAR-T based receptor increases targeting towards Non-small cell lung cancer. Paves new strategy for Syngenic cancer therapeutics. Abstract: Cell membrane-derived nanoparticles (NPs) have recently gained popularity due to their desirable features in drug delivery such as mimicking properties of native cells, impeding systemic clearance, and altering foreign body responses. Besides NP technology, adoptive immunotherapy has emerged due to its promise in cancer specificity and therapeutic efficacy. In this research, we developed a biomimetic drug carrier based on chimeric antigen receptor (CAR) transduced T-cell membranes. For that purpose, anti-HER2 CAR-T cells were engineered via lentiviral transduction of anti-HER2 CAR coding lentiviral plasmids. Anti-HER2 CAR-T cells were characterized by their specific activities against the HER2 antigen and used for cell membrane extraction. Anti-cancer drug Cisplatin-loaded poly (D, l-lactide-co-glycolic acid) (PLGA) NPs were coated with anti-human epidermal growth factor receptor 2 (HER2)-specific CAR engineered T-cell membranes. Anti-HER2 CAR-T-cell membrane-coated PLGA NPs (CAR-T-MNPs) were characterized and confirmed via fluorescent microscopy and flow cytometry. Membrane-coated NPs showed a sustained drug release over the course of 21 days in physiological conditions. Cisplatin-loaded CAR-T-MNPs also inhibited the growth of multiple HER2+ cancer cells in vitro. In addition, in vitro uptake studies revealed that CAR-T-MNPs showed an increased uptake by A549 cells. These results were also confirmed via in vivo biodistribution and therapeutic studies using a subcutaneous lung cancer model in nude mice. CAR-T-MNPs localized preferentially at tumor areas compared to those of other studied groups and consisted of a significant reduction in tumor growth in tumor-bearing mice. In Conclusion, the new CAR modified cell membrane-coated NP drug-delivery platform has demonstrated its efficacy both in vitro and in vivo. Therefore, CAR engineered membrane-coated NP system could be a promising cell-mimicking drug carrier that could improve therapeutic outcomes of lung cancer treatments.”

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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a​ free ​scientific/​networking conference hosted by Akina (http://bprconference.com/​).

PEG-PLGA from PolySciTech used in development of nanoparticles to treat stroke-induced brain injury

Friday, January 12, 2024, 2:04 PM ET

In 2021, 1 out of every 6 deaths from cardiovascular disease was caused by stroke and 87% of all strokes are ischemic strokes (https://www.cdc.gov/stroke/facts.htm). In addition to loss of blood-flow during ischemic stroke, brain damage is further aggravated by inflammation and other physiological responses. By reducing the inflammatory response, the damage from a stroke can be mitigated. Researchers at Chungnam National University, The University of Alabama, Mayo Clinic, Dankook University, Kyungpook National University, Indiana University School of Medicine, Seoul National University, Hallym University, Konyang University, Ajou University, Chungnam National University, and The University of Alabama used PLGA-PEG-COOH (AI078) and mPEG-PLGA (AK037) from PolySciTech Division of Akina, Inc (www.polyscitech.com) to develop nanoparticles decorated with AstroLa peptide for targeting to stroke-damaged portions of the brain and reducing inflammation. This research holds promise to reduce the damage resulting from an often fatal disease. Read more: Shin, Hyo Jung, Seung Gyu Choi, Fengrui Qu, Min-Hee Yi, Choong-Hyun Lee, Sang Ryong Kim, Hyeong-Geug Kim et al. "Peptide-mediated targeted delivery of SOX9 nanoparticles into astrocytes ameliorates ischemic brain injury." Nanoscale (2024). https://pubs.rsc.org/en/content/articlehtml/2023/nr/d3nr01318a

“Abstract: Astrocytes are highly activated following brain injuries, and their activation influences neuronal survival. Additionally, SOX9 expression is known to increase in reactive astrocytes. However, the role of SOX9 in activated astrocytes following ischemic brain damage has not been clearly elucidated yet. Therefore, in the present study, we investigated the role of SOX9 in reactive astrocytes using a poly-lactic-co-glycolic acid (PLGA) nanoparticle plasmid delivery system in a photothrombotic stroke animal model. We designed PLGA nanoparticles to exclusively enhance SOX9 gene expression in glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes. Our observations indicate that PLGA nanoparticles encapsulated with GFAP:SOX9:tdTOM reduce ischemia-induced neurological deficits and infarct volume through the prostaglandin D2 pathway. Thus, the astrocyte-targeting PLGA nanoparticle plasmid delivery system provides a potential opportunity for stroke treatment. Since the only effective treatment currently available is reinstating the blood supply, cell-specific gene therapy using PLGA nanoparticles will open a new therapeutic paradigm for brain injury patients in the future.”

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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a​ free ​scientific/​networking conference hosted by Akina (http://bprconference.com/​).

PLGA from PolySciTech used for temporary fluorescent marking of patients for record keeping to prevent medical errors.

Friday, January 12, 2024, 2:03 PM ET

Studies of medical errors indicate that as many as 251,000 deaths occur annually in the United States as a result of these errors (https://pubmed.ncbi.nlm.nih.gov/28186008/). Tools which enable easy, quick, and temporary recording of patient data can reduce these errors. Researchers at Massachusetts Institute of Technology, University of Melbourne, and Global Health Labs used PLGA (AP022) from PolySciTech Division of Akina, Inc (www.polyscitech.com) to create quantum-dot loaded microneedles. These provide for a fluorescent tracer embedded in patient skin which slowly degrades away after the mark is no longer needed. By coding this marker to represent relevant patient health data, costly and potentially dangerous medical mistakes can be prevented. Read more: Collins, Joe, Jooli Han, Morteza Sarmadi, Stephanie Allison‐Logan, Aurelien vander Straeten, Collin F. Perkinson, Sarah Acolaste et al. "On‐Patient Temporary Medical Record for Accurate, Time‐Sensitive Information at the Point of Care." Advanced Functional Materials (2024): 2311821. https://onlinelibrary.wiley.com/doi/pdf/10.1002/adfm.202311821

“Accurate medical recordkeeping is important for personal and public health. Conventional forms of on-patient medical information, such as medical alert bracelets or finger-markings, may compromise patient privacy because they are readily visible to other people. Here, the development of an invisible, temporary, and easily deployable on-patient medical recordkeeping system is reported. Information is stored in unique patterns of spatially distributed near-infrared (NIR) fluorescent quantum dots (QDs), which are delivered to the skin using dissolvable microneedle arrays. The patterns are invisible to the naked eye but detectable with an infrared camera, which can extract information with >98% accuracy using automated pattern recognition software. By encapsulating NIR QDs in an FDA-approved biodegradable polymer, biodegradation rates can be tuned so that the encoded medical information can be conveyed in both a spatial and temporal manner, with some components fading within 100 days and others persisting for 6 months. This may be particularly useful for administering a series of vaccinations or treatments by indicating if enough time has passed for the patient to receive the next dose. Importantly, this system contains no personal information, does not require connection to a centralized database, and is not visible to the naked eye, ensuring patient privacy.”

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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a​ free ​scientific/​networking conference hosted by Akina (http://bprconference.com/​).

PLGA from PolySciTech used in development of printable antibiotic coatings for orthopedic implants

Wednesday, January 3, 2024, 11:48 AM ET

Infections associated with surgical implantation can lead to significant patient morbidity and costs for extended treatment of the bacterial infection. The incidence of this varies but has been reported to be ~ 5.3% of cases with Staphylococcus aureus being the most common bacteria (https://pubmed.ncbi.nlm.nih.gov/28712173/). Researchers at Warsaw University of Technology, University of Helsinki, and Medical University of Warsaw used PLGA (AP081, AP041) from PolySciTech Division of Akina, Inc (www.polyscitech.com) to create a printable formulation of antimicrobial releasing surface coating for orthopedic implants. This research holds promise to reduce surgical infections from implant placement. Martinez Perez, David, Ines Reigada, Jayendra Z Patel, Jari Yli-Kauhaluoma, Leena Hanski, Michał Srebrzynski, Maciej Spychalski, Emilia Choinska, Adyary Fallarero, and Wojciech Święszkowski. "Drop on Demand Antimicrobial Printed Coatings Loaded with Dehydroabietic Acid Derivative to Prevent Orthopedic Implant Infections." Available at SSRN 4633087. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4633087

“For the first time, microvalve-based drop on demand (DOD) printing technology has been applied to develop antimicrobial coatings for orthopedic implants. Leveraging the highprecision deposition capabilities of DOD, coatings loaded with a novel biofilm inhibitor, N- (abiet-8,11,13-trien-18-oyl) cyclohexyl-L-alanine (DHA1), were fabricated on titanium coupons. The PLGA-PEG-DHA1 coatings exhibited significant efficacy in preventing Staphylococcus aureus adhesion, both in monoculture and in co-culture with HL-60 cells. Furthermore, the PLGA-PEGDHA1 coatings showed a sustained protective effect of the 30% DHA1-loaded coating over a 24- hour period. The PLGA-PEG-DHA1 coatings ensured safety with no cytotoxic effect observed on SaOS-2 mammalian cells, fostering tissue integration post-implantation. This study paves the way to produce multi-component DOD coatings combining various ink compositions, including different polymers, antimicrobial agents, or growth factors.”

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PLGA-Rhodamine used in development of macrophage backpacks for anti-inflammatory applications

Monday, December 18, 2023, 4:21 PM ET

Brain injury is often made worse by subsequent inflammation which exasperates existing damage. Mitigating this inflammation can provide a valuable tool for trauma treatment. Researchers at Harvard University and Massachusetts General Hospital used PLGA-Rhodamine (cat# AV011) from PolySciTech division of Akina, Inc. (www.polyscitech.com) as part of development of immune-cell targeting particles for treatment of inflammation. This research holds promise to treat excess inflammation and subsequent damage. Kapate, Neha, Rick Liao, Ryan Luke Sodemann, Tawny Stinson, Supriya Prakash, Ninad Kumbhojkar, Vineeth Chandran Suja et al. "Backpack-mediated anti-inflammatory macrophage cell therapy for the treatment of traumatic brain injury." PNAS Nexus (2023): pgad434. https://academic.oup.com/pnasnexus/advance-article-pdf/doi/10.1093/pnasnexus/pgad434/54408201/pgad434.pdf

“Abstract: Traumatic brain injury (TBI) is a debilitating disease with no current therapies outside of acute clinical management. While acute, controlled inflammation is important for debris clearance and regeneration after injury, chronic, rampant inflammation plays a significant adverse role in the pathophysiology of secondary brain injury. Immune cell therapies hold unique therapeutic potential for inflammation modulation, due to their active sensing and migration abilities. Macrophages are particularly suited for this task, given the role of macrophages and microglia in the dysregulated inflammatory response after TBI. However, maintaining adoptively transferred macrophages in an anti-inflammatory, wound-healing phenotype against the pro-inflammatory TBI milieu is essential. To achieve this, we developed discoidal microparticles, termed backpacks, encapsulating anti-inflammatory interleukin-4 and dexamethasone for ex vivo macrophage attachment. Backpacks durably adhered to the surface of macrophages without internalization and maintained an anti-inflammatory phenotype of the carrier macrophage through 7 days in vitro. Backpack-macrophage therapy was scaled up and safely infused into piglets in a cortical impact TBI model. Backpack-macrophages migrated to the brain lesion site and reduced pro-inflammatory activation of microglia in the lesion penumbra of the rostral gyrus of the cortex and decreased serum concentrations of pro-inflammatory biomarkers. These immunomodulatory effects elicited a 56% decrease in lesion volume. The results reported here demonstrate, to the best of our knowledge, the first use of a cell therapy intervention for a large animal model of TBI and highlight the potential of macrophage-based therapy. Further investigation is required to elucidate the neuroprotection mechanisms associated with anti-inflammatory macrophage therapy.”

PLGA-Rhodamine from PolySciTech used in research on magnetic nanoparticles for magnetic-based cellular targeting.

Wednesday, December 13, 2023, 3:32 PM ET

One way to deliver drugs to the desired location in a body is to attach them via small particles, or backpacks, to macrophage cells which are travelling to that section. Notably, this can be utilized to treat cancer which is highly difficult to get drug molecules into the right location. Researchers at University of Colorado Boulder, University of Florida used PLGA-Rhodamine (AV011) from PolySciTech division of Akina, Inc. (www.polyscitech.com) as part of creating magnetic backpacks to specifically bind to cellular components. This research holds promise to provide for an additional cancer treatment option. Read more: Day, Nicole B., Christopher R. Orear, Ambar C. Velazquez-Albino, Hayden J. Good, Andrii Melnyk, Carlos M. Rinaldi-Ramos, and C. Wyatt Shields IV. "Magnetic Cellular Backpacks for Spatial Targeting, Imaging, and Immunotherapy." ACS Applied Bio Materials (2023). https://pubs.acs.org/doi/abs/10.1021/acsabm.3c00720

“Adoptive cell transfer (ACT) therapies are growing in popularity due to their ability to interact with diseased tissues in a specific manner. Disc-shaped particles, or “backpacks”, that bind to cellular surfaces show promise for augmenting the therapeutic potential of adoptively transferred cells by resisting phagocytosis and locally releasing drugs to maintain cellular activity over time. However, many ACTs suffer from limited tumor infiltration and retention and lack a method for real-time spatial analysis. Therefore, we have designed biodegradable backpacks loaded with superparamagnetic iron oxide nanoparticles (SPIONs) to improve upon current ACT strategies by (i) controlling the localization of cell-backpack complexes using gradient magnetic fields and (ii) enabling magnetic particle imaging (MPI) to track complexes after injection. We show that magnetic backpacks bound to macrophages and loaded with a proinflammatory drug, resiquimod, maintain anticancer phenotypes of carrier macrophages for 5 days and create cytokine “factories” that continuously release IL-12. Furthermore, we establish that forces generated by gradient magnet fields are sufficient to displace cell-backpack complexes in physiological settings. Finally, we demonstrate that MPI can be used to visualize cell-backpack complexes in mouse tumors, enabling a potential strategy to track the biodistribution of ACTs in real time. KEYWORDS: adoptive cell transfer immunotherapy cancer drug delivery macrophage microparticle magnetic particle imaging”

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Development-grade polymer products from Ashland, available through PolySciTech, used for in-situ gel research

Thursday, December 7, 2023, 2:32 PM ET

Development grade PLGA, PLA, and PCL from Ashland is now available via distribution partnership with Akina, Inc. You can see the available products here (https://akinainc.com/polyscitech/products/ashland/). These polymers have been used in several projects including research done at Temple University where they used PLGA (cat# AS002, DLG5003A) to create in-situ gels. This research holds promise to improve drug-delivery options in the future. Zhang, Qiangnan, and Reza Fassihi. "Release rate determination from in situ gel forming PLGA implant: A novel ‘shape-controlled basket in tube’method." Journal of Pharmacy and Pharmacology 72, no. 8 (2020): 1038-1048. https://academic.oup.com/jpp/article-abstract/72/8/1038/6122207

“Abstract: Objectives: This study aimed to examine the impact of syringe-needle assembly differences in making implants of different shapes as well as its influence on the release kinetics and investigate the release kinetics of the in situ forming implant under various release arrangements. Methods: PLGA in situ forming implant was prepared in different shape and then subjected to in vitro release testing. Mathematical modelling was used to investigate drug release mechanisms. Key findings: The in situ forming implant was investigated for the first time how implant shapes can affect release results. It was demonstrated that implant shape differences could lead to significant variation in the release data. Here, we addressed this issue by developing a shape-controlled method to provide a consistent surface to volume ratio and, therefore, a reliable release result. Injectability in the in vitro release was discussed for the first time. Comparisons between various release methods were also evaluated. The release arrangement was found to be of great importance in release kinetics. Conclusions: The developed ‘shape-controlled basket in tube’ method can provide the most reproducible release profiles by minimizing implant adhesion to the release vessels or movement without sacrificing full contact between the release medium and the implant surface. Keywords: controlled and sustained release systems, dosage form design and characterization, pharmaceutics and drug delivery”

mPEG-PCL from PolySciTech used in development of SiRNA targeted delivery for cancer therapy

Wednesday, December 6, 2023, 1:07 PM ET

One strategy to treat cancer is to modify the tumor microenvironment so that the immune system is more likely to attack the cancer. Researchers at Ludwig-Maximilians-University Munich, Daiichi Sankyo Europe GmbH, University of Augsburg, Nanotemper Technologies GmbH, University of Augsburg, and Daiichi Sankyo Europe GmbH used mPEG-PCL (cat# AK073) from PolySciTech division of Akina, Inc. (www.polyscitech.com) as part of research into SiRNA delivery to macrophages. This research holds promise to improve therapy against cancer. Read more: Jürgens, David C., Benjamin Winkeljann, Miriam Kolog Gulko, Yao Jin, Judith Möller, Joshua Winkeljann, Sahana Sheshachala et al. "Efficient and Targeted siRNA Delivery to M2 Macrophages by Smart Polymer Blends for M1 Macrophage Repolarization as a Promising Strategy for Future Cancer Treatment." ACS Biomaterials Science & Engineering (2023). https://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.3c01595

“Cancer remains an issue on a global scale. It is estimated that nearly 10 million people succumbed to cancer worldwide in 2020. New treatment options are urgently needed. A promising approach is a conversion of tumor-promoting M2 tumor-associated macrophages (TAMs) as part of the tumor microenvironment to tumor-suppressive M1 TAMs by small interfering RNA (siRNA). In this work, we present a well-characterized polymeric nanocarrier system capable of targeting M2 TAMs by a ligand–receptor interaction. Therefore, we developed a blended PEI-based polymeric nanoparticle system conjugated with mannose, which is internalized after interaction with macrophage mannose receptors (MMRs), showing low cytotoxicity and negligible IL-6 activation. The PEI–PCL–PEI (5 kDa–5 kDa–5 kDa) and Man-PEG–PCL (2 kDa–2 kDa) blended siRNA delivery system was optimized for maximum targeting capability and efficient endosomal escape by evaluation of different polymer and N/P ratios. The nanoparticles were formulated by surface acoustic wave-assisted microfluidics, achieving a size of ∼80 nm and a zeta potential of approximately +10 mV. Special attention was given to the endosomal escape as the so-called bottleneck of RNA drug delivery. To estimate the endosomal escape capability of the nanocarrier system, we developed a prediction method by evaluating the particle stability via the inflection temperature. Our predictions were then verified in an in vitro setting by applying confocal microscopy. For cellular experiments, however, human THP-1 cells were polarized to M2 macrophages by cytokine treatment and validated through MMR expression. To show the efficiency of the nanoparticle system, GAPDH and IκBα knockdown was performed in the presence or absence of an MMR blocking excess of mannan. Cellular uptake, GAPDH knockdown, and NF-κB western blot confirmed efficient mannose targeting. Herein, we presented a well-characterized nanoparticle delivery system and a promising approach for targeting M2 macrophages by a mannose–MMR interaction. KEYWORDS: M2 tumor-associated macrophages siRNA macrophage mannose receptors microfluidics surface acoustic waves polymer blends”

Customized PLGA from PolySciTech used in comparative research on dexamethasone delivery rod formulation

Tuesday, November 21, 2023, 3:09 PM ET

The release rate of drug from any PLGA-based system is controlled by several parameters including the properties of the PLGA polymer used for the system. Although this is well known, the correlation between polymer properties and drug release is not well understood. Researchers at University of Texas at Austin and US Food and Drug Administration used customized PLGA from PolySciTech division of Akina, Inc. (www.polyscitech.com) with specified blockiness (lactide-glycolide block length) to investigate the effect of PLGA properties on drug release. This research lays the foundation for correlating PLGA properties to product performance. Read more: Costello, Mark A., Joseph Liu, Louise Kuehster, Yan Wang, Bin Qin, Xiaoming Xu, Qi Li, William C. Smith, Nathaniel A. Lynd, and Feng Zhang. "Role of PLGA Variability in Controlled Drug Release from Dexamethasone Intravitreal Implants." Molecular Pharmaceutics (2023). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.3c00742

“Long-acting injectable formulations based on poly(lactide-co-glycolide) (PLGA) have been commercialized for over 30 years in at least 20 FDA-approved products. These formulations offer several advantages, including reduced dosing frequency, improved patient compliance, and maintenance of therapeutic levels of drug. Despite extensive studies, the inherent complexity of the PLGA copolymer still poses significant challenges associated with the development of generic formulations having drug release profiles equivalent to those of the reference listed drugs. In addition, small changes to PLGA physicochemical properties or the drug product manufacturing process can have a major impact on the drug release profile of these long-acting formulations. This work seeks to better understand how variability in the physicochemical properties of similar PLGAs affects drug release from PLGA solid implants using Ozurdex (dexamethasone intravitreal implant) as the model system. Four 50:50, acid-terminated PLGAs of similar molecular weights were used to prepare four dexamethasone intravitreal implants structurally equivalent to Ozurdex. The PLGAs were extensively characterized by using a variety of analytical techniques prior to implant manufacture using a continuous, hot-melt extrusion process. In vitro release testing of the four structurally equivalent implants was performed in both normal saline and phosphate-buffered saline (PBS), yielding drastically different results between the two methods. In normal saline, no differences in the release profiles were observed. In PBS, the drug release profiles were sensitive to small changes in the residual monomer content, carboxylic acid end group content, and blockiness of the polymers. This finding further underscores the need for a physiologically relevant in vitro release testing method as part of a robust quality control strategy for PLGA-based solid implant formulations. KEYWORDS: PLGA, implant, Ozurdex, hot-melt extrusion, blockiness, acid number”

PLGA-PEG-Azide from PolySciTech used in development of nanoparticles for delivery of SiRNA delivery system

Wednesday, November 15, 2023, 2:00 PM ET

Silencing RNA has the ability to act as a selective gene expression modifier, turning off or negating the effect of specific gene expression on demand. This can be a useful tool for a wide range of disease states however suffers from several drawbacks including SiRNA’s susceptibility to degradation which makes delivery of it to cells difficult. Researchers at Northwestern University used PLGA-PEG-Azide (cat# AI085) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to develop particles for delivery of SiRNA to cells. This research holds promise to improve SiRNA delivery. Read more: Park, Jungsoo, Michael Evangelopoulos, Matthew Kuo Vasher, Sergej Kudruk, Namrata Ramani, Vinzenz Mayer, Alexander Carlos Solivan, Andrew Lee, and Chad Alexander Mirkin. "Enhancing Endosomal Escape and Gene Regulation Activity for Spherical Nucleic Acids." Small (2023): 2306902. https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.202306902

“The therapeutic potential of small interfering RNAs (siRNAs) is limited by their poor stability and low cellular uptake. When formulated as spherical nucleic acids (SNAs), siRNAs are resistant to nuclease degradation and enter cells without transfection agents with enhanced activity compared to their linear counterparts; however, the gene silencing activity of SNAs is limited by endosomal entrapment, a problem that impacts many siRNA-based nanoparticle constructs. To increase cytosolic delivery, SNAs are formulated using calcium chloride (CaCl2) instead of the conventionally used sodium chloride (NaCl). The divalent calcium (Ca2+) ions remain associated with the multivalent SNA and have a higher affinity for SNAs compared to their linear counterparts. Importantly, confocal microscopy studies show a 22% decrease in the accumulation of CaCl2-salted SNAs within the late endosomes compared to NaCl-salted SNAs, indicating increased cytosolic delivery. Consistent with this finding, CaCl2-salted SNAs comprised of siRNA and antisense DNA all exhibit enhanced gene silencing activity (up to 20-fold), compared to NaCl-salted SNAs regardless of sequence or cell line (U87-MG and SK-OV-3) studied. Moreover, CaCl2-salted SNA-based forced intercalation probes show improved cytosolic mRNA detection.”

PLGA from PolySciTech used in development of anti-inflammatory P7C3 delivery system for wound-healing

Wednesday, November 1, 2023, 2:53 PM ET

There are several steps along the inflammation pathway and this bodily response often delays or prevents the progression of wound-healing. Targeted prevention of inflammation can be leveraged to provide for treatment of a wide range of disease states. Researchers at University of South Florida and St. John Fisher University used PLGA (cat# AP040) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create P7C3 delivery nanoparticle and tested these for delivery of this potent, anti-inflammatory compound. This research holds promise to provide treatment for inflammatory diseases. Read more: Sutariya, Vijaykumar, Priyanka Bhatt, Aren Saini, Abraian Miller, Sachin L. Badole, Jared Tur, Mackenzie Gittinger, Joung Woul Kim, Ravikumar Manickam, and Srinivas M. Tipparaju. "Development and testing of nanoparticles delivery for P7C3 small molecule using injury models." Molecular and Cellular Biochemistry (2023): 1-17. https://link.springer.com/article/10.1007/s11010-023-04865-2

“The use of nanoparticles (NPs) has emerged as a potential tool for safe and effective drug delivery. In the present study, we developed small molecule P7C3-based NPs and tested its efficacy and toxicity along with the tissue specific aptamer-modified P7C3 NPs. The P7C3 NPs were prepared using poly (D, L-lactic-co-glycolic acid) carboxylic acid (PLGA-COOH) polymer, were conjugated with skeletal muscle-specific RNA aptamer (A01B P7C3 NPs) and characterized for its cytotoxicity, cellular uptake, and wound healing in vitro. The A01B P7C3 NPs demonstrated an encapsulation efficiency of 30.2 ± 2.6%, with the particle size 255.9 ± 4.3 nm, polydispersity index of 0.335 ± 0.05 and zeta potential of + 10.4 ± 1.8mV. The FTIR spectrum of P7C3 NPs displayed complete encapsulation of the drug in the NPs. The P7C3 NPs and A01B P7C3 NPs displayed sustained drug release in vitro for up to 6 days and qPCR analysis confirmed A01B aptamer binding to P7C3 NPs. The C2C12 cells viability assay displayed no cytotoxic effects of all 3 formulations at 48 and 72 h. In addition, the cellular uptake of A01B P7C3 NPs in C2C12 myoblasts demonstrated higher uptake. In vitro assay mimicking wound healing showed improved wound closure with P7C3 NPs. In addition, P7C3 NPs significantly decreased TNF-α induced NF-κB activity in the C2C12/NF-κB reporter cells after 24-hour treatment. The P7C3 NPs showed 3-4-fold higher efficacy compared to P7C3 solutions in both wound-closure and inflammation assays in C2C12 cells. Furthermore, the P7C3 NPs showed 3-4-fold higher efficacy in reducing the infarct size and protected mouse hearts from ex vivo ischemia-reperfusion injury. Overall, this study demonstrates the safe and effective delivery of P7C3 NPs. Keywords P7C3 · P7C3 nanoparticles · A01B RNA aptamer-conjugated P7C3 nanoparticles · Sustained release · Targeted delivery · Skeletal and cardiac muscle”

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PLGA-PEG-Azide and other polymers from PolySciTech used to create colon-targeting delivery system for treatment of ulcerative colitis

Wednesday, November 1, 2023, 2:51 PM ET

Ulcerative colitis is an autoimmune disease in which the body attacks parts of the colon or natural flora. Typical treatment with systemic immunosuppressants leads to significant side-effects. Researchers at University of North Carolina at Chapel Hill and University of Texas Southwestern Medical Center used PLGA (AP045), mPEG-PLGA (AK029), PLGA-CY5 (AV034) and PLGA-PEG-N3 (AI085) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create a delivery system targeting the colon and reduce autoinflammation. This research holds promise to provide improved treatment against this chronic disease. Read more: Au, Kin Man, Justin Wilson, Jenny Ting, and Andrew Wang. "An Injectable Subcutaneous Colon-Specific Immune Niche For The Treatment Of Ulcerative Colitis." bioRxiv (2023): 2023-10. https://www.biorxiv.org/content/10.1101/2023.10.03.560652.abstract

“As a chronic autoinflammatory condition, ulcerative colitis is often managed via systemic immunosuppressants. Here we show, in three mouse models of established ulcerative colitis, that a subcutaneously injected colon-specific immunosuppressive niche consisting of colon epithelial cells, decellularized colon extracellular matrix, and nanofibers functionalized with programmed death-ligand 1, CD86, a peptide mimic of transforming growth-factor-beta 1, and the immunosuppressive small molecule leflunomide, induced intestinal immunotolerance and reduced inflammation in the animals’ lower gastrointestinal tract. The bioengineered colon-specific niche triggered autoreactive-T-cell anergy and polarized pro-inflammatory macrophages via multiple immunosuppressive pathways, and prevented the infiltration of immune cells into the colon’s lamina propria, promoting the recovery of epithelial damage. The bioengineered niche also prevented colitis-associated colorectal cancer, and eliminated immune-related colitis triggered by kinase inhibitors and immune-checkpoint blockade.”

BPR (Biotech Pharma Research) Conference April 10, 2024 West Lafayette, Indiana http://bprconference.com/

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PLGA from PolySciTech used in development of virus-like particles for vaccine application

Wednesday, November 1, 2023, 2:51 PM ET

Vaccines have the potential to prevent serious infections especially those from viral sources. For rapid deployment it is ideal to have a vaccine which does not require cold-storage and can be shelf-stable for reasonable time of usage. Researchers at University of California San Diego PLGA (cat# AP041) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create nanoparticles which deliver HPV-virus like particles for improved immune-system response against a shelf-stable vaccine. This research holds promise to improve vaccine development in the future. Read more: Puente, Armando A., Oscar A. Ortega-Rivera, David M. Wirth, Jonathan K. Pokorski, and Nicole F. Steinmetz. "Melt Processing Virus-Like Particle-Based Vaccine Candidates into Biodegradable Polymer Implants." In Therapeutic Proteins: Methods and Protocols, pp. 221-245. New York, NY: Springer US, 2023. https://link.springer.com/protocol/10.1007/978-1-0716-3469-1_16

“Abstract: Melt processing is an emerging production method to efficiently encapsulate proteins into polymeric devices for sustained release. In the context of vaccines, melt processing is well-suited to develop vaccine delivery devices that are stable outside the cold chain and can generate protective immunity from a single dose. We have demonstrated the compatibility of bacteriophage Qβ virus-like particles (VLPs) with hot-melt extrusion (HME) and have leveraged this technology to develop a single-dose vaccine candidate for vaccination against human papillomavirus (HPV). Here, we detail the methods for chemically conjugating an HPV peptide epitope from the L2 minor capsid protein to Qβ VLPs to generate HPV-Qβ particles. We outline techniques used to characterize HPV-Qβ particles, and we elaborate on the process to encapsulate HPV-Qβ into biodegradable poly(lactic-co-glycolic acid) (PLGA) implants and discuss methods for the materials characterization of the HPV-Qβ/polymer melts. The methods described could be adapted to other disease targets, i.e., by conjugation of a different peptide epitope, or transferred to other VLP systems suited for conjugation, immune response, or stability during processing. Such VLPs are ideally suited for use in HME, a mature, scalable, continuous, and solvent-free process which can be adapted to mold devices, therefore allowing the processing of the melts into various geometries, such as subcutaneous implants, or self-administrable microneedle patches. Key words: Vaccines, Melt processing, Sustained release, Single-dose vaccines, Polymer implants, Virus-like particles (VLP), Human papillomavirus (HPV), Bacteriophage Qβ, L2 capsid protein”

BPR (Biotech Pharma Research) Conference April 10, 2024 West Lafayette, Indiana http://bprconference.com/

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PEG-PLA from PolySciTech used in development of ultrasound-triggered nanoparticles for controlled delivery of medicine to the brain

Tuesday, October 17, 2023, 4:55 PM ET

Nanoparticles have a wide variety of mechanisms of control, one of which is to dose ultrasound-sensitive particles systemically through the body and then utilize focused ultrasound to control their release at predetermined locations. Researchers at University of Utah used PEG-PLA (AK009) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create nanoparticles which are sensitive to ultrasound. They tested these for delivery of propofol in select locations in the brains of non-human primates. This research holds promise for controlled delivery with extreme precision. Read more: Wilson, Matthew Gray, Taylor D. Webb, Henrik Odéen, and Jan Kubanek. "Remotely controlled drug release in deep brain regions of non-human primates." bioRxiv (2023): 2023-10. https://www.biorxiv.org/content/10.1101/2023.10.09.561539.abstract

“Many areas of science and medicine would benefit from selective release of drugs in specific regions of interest. Nanoparticle drug carriers activated by focused ultrasound—remotely applied, depth-penetrating energy—may provide such selective interventions. Here, we developed stable, ultrasound-responsive nanoparticles that can be used to release drugs effectively and safely in non-human primates. The nanoparticles were used to release propofol in deep brain visual regions. The release reversibly modulated the subjects’ visual choice behavior and was specific to the targeted region and to the released drug. Gadolinium-enhanced MRI imaging suggested an intact blood-brain barrier. Blood draws showed normal clinical chemistry and hematology. In summary, this study provides a safe and effective approach to release drugs on demand in selected deep brain regions at levels sufficient to modulate behavior. Keywords: Drug release, ultrasound, nanoparticle carriers, pharmacomodulation, neuromodulation”

BPR (Biotech Pharma Research) Conference April 10, 2024 West Lafayette, Indiana http://bprconference.com/

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PEG-PLGA from PolySciTech used in development of FN14 targeted nanoparticles for breast cancer

Tuesday, October 17, 2023, 4:53 PM ET

Fibroblast growth factor-inducible 14 (Fn14) is a member of the tumor necrosis factor (TNF) receptor family that is induced in a variety of cell types in situations of tissue injury. This is a potent marker and an attractive target for therapeutic applications. Researchers at University of Maryland and NIH-NIDCR used PEG-PLGA (AK010) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create nanoparticles targeting Fn14. This research holds promise to improve therapy against a variety of cancers. Read more: Carney, Christine P., Nikhil Pandey, Anshika Kapur, Hassan Saadi, Hwei Ling Ong, Chixiang Chen, Jeffrey A. Winkles, Graeme F. Woodworth, and Anthony J. Kim. "Impact of Targeting Moiety Type and Protein Corona Formation on the Uptake of Fn14-Targeted Nanoparticles by Cancer Cells." ACS nano (2023). https://pubs.acs.org/doi/abs/10.1021/acsnano.3c02575

“The TWEAK receptor, Fn14, is a promising candidate for active targeting of cancer nanotherapeutics to many solid tumor types, including metastatic breast and primary brain cancers. Targeting of therapeutic nanoparticles (NPs) has been accomplished using a range of targeting moieties including monoclonal antibodies and related fragments, peptides, and small molecules. Here, we investigated a full-length Fn14-specific monoclonal antibody, ITEM4, or an ITEM4-Fab fragment as a targeting moiety to guide the development of a clinical formulation. We formulated NPs with varying densities of the targeting moieties while maintaining the decreased nonspecific adhesivity with receptor targeting (DART) characteristics. To model the conditions that NPs experience following intravenous infusion, we investigated the impact of serum exposure in relation to the targeting moiety type and surface density. To further evaluate performance at the cancer cell level, we performed experiments to assess differences in cellular uptake and trafficking in several cancer cell lines using confocal microscopy, imaging flow cytometry, and total internal reflection fluorescence microscopy. We observed that Fn14-targeted NPs exhibit enhanced cellular uptake in Fn14-high compared to Fn14-low cancer cells and that in both cell lines uptake levels were greater than observed with control, nontargeted NPs. We found that serum exposure increased Fn14-targeted NP specificity while simultaneously reducing the total NP uptake. Importantly, serum exposure caused a larger reduction in cancer cell uptake over time when the targeting moiety was an antibody fragment (Fab region of the monoclonal antibody) compared with the full-length monoclonal antibody targeting moiety. Lastly, we uncovered that full monoclonal antibody-targeted NPs enter cancer cells via clathrin-mediated endocytosis and traffic through the endolysosomal pathway. Taken together, these results support a pathway for developing a clinical formulation using a full-length Fn14 monoclonal antibody as the targeting moiety for a DART cancer nanotherapeutic agent. KEYWORDS: fibroblast growth factor-inducible-14 (Fn14) targeting DART nanoparticle protein corona glioma glioblastoma triple-negative breast cancer”

BPR (Biotech Pharma Research) Conference April 10, 2024 West Lafayette, Indiana http://bprconference.com/

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PLGA-PEG derivatives from PolySciTech used in development of targeted nanoparticle for treatment of type-1 diabetes

Thursday, October 12, 2023, 1:21 PM ET

Approximately 1.9 million Americans have type 1 diabetes (diabetes.org), a chronic condition in which the pancreas produces little or no insulin. One way to target nanoparticles is to functionalize them with a particular ligand, although typically a peptide or protein any molecule which provides good binding can be used for this. Researchers at Universidade do Porto and Universidade do Minho used PLGA-PEG-COOH (AI171), PLGA-PEG-Mal (AI110), and PLGA-Rhodamine (AV011) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create nanoparticles surface functionalized with exenatide (GLP1 binding) for delivery of peptide therapy to the pancreatic-based insulin system. This research holds promise for improved treatment of diabetes in the future. Read more: Cristelo, Cecília, Rute Nunes, Soraia Pinto, Joana Moreira Marques, Francisco Miguel Gama, and Bruno Sarmento. "Targeting β Cells with Cathelicidin Nanomedicines Improves Insulin Function and Pancreas Regeneration in Type 1 Diabetic Rats." ACS Pharmacology & Translational Science (2023). https://pubs.acs.org/doi/abs/10.1021/acsptsci.3c00218

“Type 1 diabetes (T1D) is an incurable condition with an increasing incidence worldwide, in which the hallmark is the autoimmune destruction of pancreatic insulin-producing β cells. Cathelicidin-based peptides have been shown to improve β cell function and neogenesis and may thus be relevant while developing T1D therapeutics. In this work, a cathelicidin-derived peptide, LLKKK18, was loaded in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), surface-functionalized with exenatide toward a GLP-1 receptor, aiming the β cell-targeted delivery of the peptide. The NPs present a mean size of around 100 nm and showed long-term stability, narrow size distribution, and negative ζ-potential (−10 mV). The LLKKK18 association efficiency and loading were 62 and 2.9%, respectively, presenting slow and sustained in vitro release under simulated physiologic fluids. Glucose-stimulated insulin release in the INS-1E cell line was observed in the presence of the peptide. In addition, NPs showed a strong association with β cells from isolated rat islets. After administration to diabetic rats, NPs induced a significant reduction of the hyperglycemic state, an improvement in the pancreatic insulin content, and glucose tolerance. Also remarkable, a considerable increase in the β cell mass in the pancreas was observed. Overall, this novel and versatile nanomedicine showed glucoregulatory ability and can pave the way for the development of a new generation of therapeutic approaches for T1D treatment.”

BPR (Biotech Pharma Research) Conference April 10, 2024 West Lafayette, Indiana. Free, 1-day scientific/networking conference, see more here http://bprconference.com/

Akina is hiring, see employment opportunities here: http://akinainc.com/employment.php

BPR (Biotech Pharma Research) Conference

Thursday, October 12, 2023, 8:20 AM ET

Wednesday, April 10, 2024

9:00 AM - 4:30 PM

After a pandemic hiatus, Akina is proud to bring back West Lafayette's premier scientific/networking conference. This conference is available free of charge thanks to sponsorship by Akina, Inc. and Miftek Corporation with opportunities to present as well as exhibit. The BPR Conference is an excellent opportunity to form connections with companies and individuals in the Greater Lafayette, Indiana area as well as promote your services/offerings, forge employment connections, and so much more.

Request your table-top booth space and/or a speaker slot, and register to attend now! BPRconference.com

PLCL from PolySciTech used in development of minimally invasive implantable cortical interface

Friday, September 29, 2023, 12:45 PM ET

Interfacing the brain with a computer typically requires a highly invasive surgical procedure to provide for electrical contacts to the brain. Researchers at Seoul National University, Ulsan National Institute of Science and Technology, Dankook University, Kwangwoon University, Korea Institute of Science and Technology (KIST), Asan Medical Center used PLCL (Cat# AP067) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to make a membrane which can be implanted through a small insertion and allow for brain-computer interface. This research holds promise for treatment of neuropathic brain disorders and other disease states. Read more: Kang, Seung-Kyun, Jae-Young Bae, Gyeong-Seok Hwang, Young-Seo Kim, Jooik Jeon, Min-Seong Chae, Joon-Woo Kim et al. "Fully-Biodegradable and Self-Deployable Electronic Tent for Brain Cortex." (2023). https://www.researchsquare.com/article/rs-3324850/latest

“The large-area and high-density electronic interfaces for the cortex stands as a crucial enabler for brain-computer interfaces, facilitating synchronization between cognitive functions and motor activities, as well as aiding in the diagnosis neuropathic brain disorders in the realm of cognitive neuroscience and clinical neurology. Nevertheless, the current implantation procedures pose significant challenges that, subject patients to invasiveness throughout the entire interventional procedure. Here, we introduce a fully-biodegradable and self-deployable platform with multimodal inorganic electronics, which can be programmably-packaged and self-deployed using syringe for minimally invasive delivery through a small hole. After use, it naturally decomposes within the body, minimizing invasiveness from initial insertion surgery to subsequent removal. In vivo demonstration shows the potential of minimally invasive cortical-interfacing platform for manipulating large areas of cortical activities.”

BPR Conference (April 10, 2024) Akina, Inc. is hosting a Scientific/Networking conference for companies in the Biotechnology, Pharmaceutics, and Research sector. This 1-day conference is free to attend and hosted in Purdue Research Park’s KPTC center. See more and register here: http://bprconference.com/

Video: https://youtu.be/LenZaGa7rwg

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.23907899856567 seconds)


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