Thursday, February 22, 2024

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

 



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/).

Friday, February 16, 2024

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

 


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

 

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

 


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/​).

Tuesday, February 6, 2024

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

 


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/​).

Wednesday, January 31, 2024

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

 

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

Video: https://youtu.be/wpexfgqfnL0

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

 

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

Video: https://youtu.be/SCy96Ils4PQ