John Garner's Technical Blog
John GarnerJohn Garner, Manager

What's New and on the Manager's Mind

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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PLGA from PolySciTech used in development of nanoparticle system for lung-cancer

Thursday, February 20, 2020, 2:39 PM ET

Many chemotherapeutic agents, such as cisplatin, are highly toxic which limits the dose due to side effects. A delivery system which can improve the amount of drug which actually releases in the tumor site would improve this. Recently, researchers at University of Texas used PLGA (AP154) from PolySciTech (www.polyscitech.com) was used to create cisplatin-loaded PLGA nanoparticles for comparison to novel PEU nanoparticles. This research holds promise to provide for improved therapies against lung cancer. Read more: Iyer, Roshni, Tam Nguyen, Dona Padanilam, Cancan Xu, Debabrata Saha, Kytai T. Nguyen, and Yi Hong. "Glutathione-responsive biodegradable polyurethane nanoparticles for lung cancer treatment." Journal of Controlled Release (2020). https://www.sciencedirect.com/science/article/pii/S0168365920301115

“Highlights: Glutathione is abundantly available in lung cancer microenvironment. Biodegradable polyurethane nanoparticles were fabricated via a single emulsion with a mixed organic solvent. GSH-sensitive biodegradable polyurethane nanoparticles (GPUs) released encapsulated cisplatin in response to elevated glutathione levels. Cisplatin loaded GPUs significantly reduced tumor growth in a subcutaneously xenograft A549 lung tumor mouse model compared to the free cisplatin. Abstract: Lung cancer is one of the major causes of cancer-related deaths worldwide. Stimuli-responsive polymers and nanoparticles, which respond to exogenous or endogenous stimuli in the tumor microenvironment, have been widely investigated for spatiotemporal chemotherapeutic drug release applications for cancer chemotherapy. We developed glutathione (GSH)-responsive polyurethane nanoparticles (GPUs) using a GSH-cleavable disulfide bond containing polyurethane that responds to elevated levels of GSH within lung cancer cells. The polyurethane nanoparticles were fabricated using a single emulsion and mixed organic solvent method. Cisplatin-loaded GSH-sensitive nanoparticles (CGPU) displayed a GSH-dose dependent release of cisplatin. In addition, a significant reduction in in vitro survival fraction of A549 lung cancer cells was observed compared to free cisplatin of equivalent concentration (survival fraction of ~0.5 and ~0.7, respectively). The in vivo biodistribution studies showed localization of fluorescently labeled GPUs (~7% of total injected dose) in the lung tumor regions after mouse-tail IV injections in xenograft A549 lung tumor models. The animals exposed to CGPUs also exhibited the inhibition of lung tumor growth compared to animals administered with saline (tumor growth rate of 1.5 vs. 13 in saline) and free cisplatin (tumor growth rate of 5.9) in mouse xenograft A549 lung tumor models within 14 days. These nanoparticles have potential to be used for on-demand drug release for an enhanced chemotherapy to effectively treat lung cancer.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLGA from PolySciTech used in evaluation of 3D Cell culturing of cancer cells as assay tool.

Thursday, February 13, 2020, 4:35 PM ET

Testing cancer therapies requires making sure that the test used is relevant to the physiology of the patient. Ideally, cancer cells will be grown in a 3D format, same as they are in the human body. Recently, researchers at San Jose State University used PLGA (AP042) from PolySciTech (www.polyscitech.com) to create doxorubicin nanoparticles for testing the accuracy of 3D Cell cultures. This research holds promise for improved research in cancer therapy in the future. Read more: Nimbalkar, Priya, Peter Tabada, Anuja Bokare, Jeffrey Chung, Marzieh Mousavi, Melinda Simon, and Folarin Erogbogbo. "Improving the physiological relevance of drug testing for drug-loaded nanoparticles using 3D tumor cell cultures." MRS Communications 9, no. 3 (2019): 1053-1059. https://www.cambridge.org/core/journals/mrs-communications/article/improving-the-physiological-relevance-of-drug-testing-for-drugloaded-nanoparticles-using-3d-tumor-cell-cultures/FEAC0E69F94D331886A06FFD2E854D0A

Nanoparticle-mediated drug delivery has the potential to overcome several limitations of cancer chemotherapy. Lipid polymer hybrid nanoparticles (LPHNPs) have been demonstrated to exhibit superior cellular delivery efficacy. Hence, doxorubicin (a chemotherapeutic drug)-loaded LPHNPs have been synthesized by three-dimensional (3D)-printed herringbone-patterned multi-inlet vortex mixer. This method offers rapid and efficient mixing of reactants yielding controllable and reproducible synthesis of LPHNPs. The cytotoxicity of LPHNPs is tested using two-dimensional (2D) and 3D microenvironments. Results obtained from 3D cell cultures showed major differences in cytotoxicity in comparison with 2D cultures. These results have broad implications in predicting in vitro LPHNP toxicology.

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

mPEG-PLA from PolySciTech used in development of simvastatin delivery system to treat neuroinflammation.

Thursday, February 13, 2020, 4:34 PM ET

Inflammation is a natural response to injury or infection which can also lead to significant health problems. Recently, researchers at Kent State University used mPEG-PLA (AK021) from PolySciTech (www.polyscitech.com) to create nanoparticles for intraceullular delivery of anti-inflammatory agents. This research holds promise to treate a variety of inflammatory-related disease states. Read more: Manickavasagam, Dharani, and Moses O. Oyewumi. "Internalization of particulate delivery systems by activated microglia influenced the therapeutic efficacy of simvastatin repurposing for neuroinflammation." International Journal of Pharmaceutics 570 (2019): 118690. https://www.sciencedirect.com/science/article/pii/S0378517319307355

“Abstract: We recently evaluated the suitability of polymersome delivery systems in simvastatin repurposing for treating neuroinflammation. The goal of the current study is to elucidate the therapeutic impact of particulate internalization by activated microglia on the resultant anti-inflammatory properties. Thus, we investigated the endocytic mechanism(s) involved in uptake and transport of simvastatin-loaded polymersomes by BV2 microglia cells coupled with delineation of the intracellular pathway(s) involved in regulating anti-inflammatory effects. Our data indicated that internalization of polymersome delivery systems by activated microglial BV2 cells was important in the suppression of nitric oxide (NO), TNF-α and IL-6 production. Further, we observed that the lipid raft/caveolae pathway had the most influential effect on polymersome internalization by microglia cells while clathrin-mediated endocytosis did not play a major role. Enhancement of anti-inflammatory effects of simvastatin could be attributed to inhibition of ERK1/2, JNK and AKT signaling pathways and internalization of polymersome delivery systems in activated microglia. Taken together, our data provided insights into how the intracellular trafficking of delivery systems by microglial could be a useful tool in modulating the desired anti-inflammatory effects of drugs.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLGA-rhodamine from PolySciTech used in development of antibacterial nanoparticles

Thursday, February 13, 2020, 4:34 PM ET

Bacteria have many survival strategies one of which is to hide inside of cells. Recently, researchers at Purdue University and Assiut University used PLGA-Rhodamine (AV011) and PLGA (AP020) from PolySciTech (www.polyscitech.com) to create fluorescent nanoparticles with antimicrobial peptides. These particles were found to be effective against intracellular bacteria. This research holds promise to provide for improved therapies against bacterial infections. Read more. G Elnaggar, Marwa, Hesham M Tawfeek, Aly A. Abdel-Rahman, E. Aboutaleb Ahmed, and Yoon Yeo. "Encapsulation Of Antennapedia (Penetratin) Peptide in a Polymeric Platform For Effective Treatment of Intracellular Bacteria." Bulletin of Pharmaceutical Sciences. Assiut 42, no. 1 (2019): 63-70. http://bpsa.journals.ekb.eg/article_62266.html

“Abstract: Antimicrobial peptides (AMP) and cell-penetrating peptides (CPP) are two classes of peptides that share some structural and physicochemical similarities. Antennapedia or penetratin (ANT) is one of the most known CPPs, that was proven to have antimicrobial activity against certain strains of planktonic bacteria. ANT can enter the cells but has no activity against intracellular bacteria. This is attributable to the inability of the peptide to reach bacteria reside within cellular components as well as low delivery efficiency, due to loss of activity by proteolysis and poor specificity. The aim of this work is to develop a formulation that can effectively reach and attack intracellular bacteria. To achieve this goal, ANT was encapsulated in PLGA platform as nanoparticles with the size range of 500-1000 nm, which allows for selective uptake by macrophages where bacteria mostly reside. ANT was loaded with high loading efficiency (12.7%) inspite of high water solubility. ANT-nanoparticles (ANT-NP) had no cytotoxicity on J774a.1 macrophages and were readily taken up by macrophages as confirmed by fluorescence microscopy. Antibacterial activity of ANT-NP remains to be tested against different intracellular bacteria.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLA from PolySciTech used in development of imaging agent for evaluation of Transarterial chemoembolization for liver cancer treatment

Thursday, February 13, 2020, 4:33 PM ET

Treatment of liver cancer often involves transcatheter embolization in which the artery that feeds the tumor area is sealed off to kill the cancer cells. Determining the success of the procedure requires being able to visualize if the region is correctly occluded or not which needs a suitable contrast/imaging agent. Recently, researchers from Southern University of Science and Technology, Henan University, Southern Medical University (China), and National University of Singapore used PLA (AP004) from PolySciTech to create fluorscent nanoparticles for visualizing the interior of decularilzed liver vascular structure. This research holds promise to improve the tools used to evaluate embolization procedures as part of treatment of liver cancer. Read more: Gao, Yanan, Zhihua Li, Yin Hong, Tingting Li, Xiaoyan Hu, Luyao Sun, Zhengchang Chen et al. "Decellularized liver as a translucent ex vivo model for vascular embolization evaluation." Biomaterials (2020): 119855. https://www.sciencedirect.com/science/article/pii/S0142961220301010

“Abstract: Transarterial chemoembolization (TACE) is the preferred treatment for patients with unresectable intermediate stage hepatocellular carcinoma, however currently the development of embolic agents for TACE lacks in vitro models that closely represent the sophisticated features of the organ and the vascular systems therein. In this study, we presented a new strategy using an ex vivo liver model to provide a translucent template for evaluating embolic agents of TACE. The ex vivo liver model was developed through decellularizion of rat liver organs with preserved liver-specific vasculatures and improved transmittance of the whole liver up to 23% at 550 nm. Using this model, we investigated the embolization performances of both liquid and particle-based embolic agents, including penetration depth, embolization end-points, injection pressure and spatial distribution dynamics. We found that the embolization endpoint of liquid embolic agent such as ethiodised oil was strongly dependent on the injection pressure, and the pressure quickly built up when reaching the capillary endings, which could cause embolic agent leaking and potential tissue damages. In contrast, for particle-based embolic agents such as poly-dl-lactide microparticles and CalliSpheres® beads, their embolization endpoints were mainly determined by the particle size, whereas the particle densities close to the endpoints dramatically dropped down, which with the penetration depth represented two critical factors determining the embolic distribution. Such a decellularized organ model may open a new route to visually and quantitatively characterize embolization effects of various embolotherapies. Keywords: Transarterial chemoembolization Embolic agents Decellularized liver matrix Vascular system Injection pressure”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

mPEG-PLGA from PolySciTech used in development of griffithsin-based system to prevent the spread of sexually transmitted diseases.

Thursday, February 13, 2020, 4:28 PM ET

HIV is a lethal disease which affects approximately 37.9 million people worldwide with (2018) leading to 770,000 deaths. Although less lethal, herpes is extremely common and, in the USA, roughly 25% of the population has genital herpes. Recently, researchers from University of Louisville used mPEG-PLGA (AK148) from PolyScitech (www.polyscitech.com) to generate drug-loaded fibers for protection against HIV and herpes infections. This research holds promise to provide a system which can prevent the spread of sexually transmitted diseases. Read more: Tyo, Kevin M., Amanda B. Lasnik, Longyun Zhang, Mohamed Mahmoud, Alfred B. Jenson, Joshua L. Fuqua, Kenneth E. Palmer, and Jill M. Steinbach-Rankins. "Sustained-release Griffithsin nanoparticle-fiber composites against HIV-1 and HSV-2 infections." Journal of Controlled Release (2020). https://www.sciencedirect.com/science/article/pii/S0168365920300857

“Highlights: Multilayered nanoparticle (NP)-electrospun fiber (EF) composites provided sustained-release of Griffithsin (GRFT). GRFT NPs and NP-EFs demonstrated in vitro efficacy against HIV-1 infection. NP-EF composites prevented lethal HSV-2 infection in a murine model. NP-EFs and NPs demonstrated preliminary safety in vivo, inducing negligible cytokine expression and inflammatory response. Abstract: Human immunodeficiency virus (HIV-1) and herpes simplex virus 2 (HSV-2) affect hundreds of millions of people worldwide. The antiviral lectin, Griffithsin (GRFT), has been shown to be both safe and efficacious against HSV-2 and HIV-1 infections in vivo. The goal of this work was to develop a multilayered nanoparticle (NP)-electrospun fiber (EF) composite to provide sustained-release of GRFT, and to examine its safety and efficacy in a murine model of lethal HSV-2 infection. Composites were fabricated from polycaprolactone (PCL) fibers surrounding polyethylene oxide (PEO) fibers that incorporated methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide) (mPEG-PLGA) GRFT NPs. GRFT loading and release were determined via ELISA, showing that NP-EF composites achieved high GRFT loading, and provided sustained-release of GRFT for up to 90 d. The in vitro efficacy of GRFT NP-EFs was assessed using HIV-1 pseudovirus assays, demonstrating complete in vitro protection against HIV-1 infection. Additionally, sustained-release NP-EFs, administered 24 h prior to infection, prevented against a lethal dose of HSV-2 infection in a murine model. In parallel, histology and cytokine expression from murine reproductive tracts and vaginal lavages collected 24 and 72 h post-administration were similar to untreated mice, suggesting that NP-EF composites may be a promising and safe sustained-delivery platform to prevent HSV-2 infection. Future work will evaluate the ability to provide prolonged protection against multiple virus challenges, and different administration times with respect to infection.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/)

mPEG-PLGA from PolySciTech used in development of nanotherapy against triple-negative breast cancer

Thursday, February 6, 2020, 9:45 AM ET

Triple-negative breast cancer is a specific type of breast cancer which is both aggressive in nature as well as difficult to treat by HER2 and other therapies which rely on specific markers that are not over-expressed on these cancer types. Recently, researchers at Dalhousie University (Canada) used mPEG-PLGA (AK010) from PolySciTech (www.polyscitech.com) to create piperine-loaded nanoparticles for treatment of triple-negative breast cancer. This research holds promise to provide better therapies against this potentially fatal disease. Read more: Rad, Javad Ghassemi, and David W. Hoskin. "Delivery of Apoptosis-inducing Piperine to Triple-negative Breast Cancer Cells via Co-polymeric Nanoparticles." Anticancer Research 40, no. 2 (2020): 689-694. http://ar.iiarjournals.org/content/40/2/689.abstract

“Background/Aim: Piperine, a major alkaloid of the fruit of black pepper plants, selectively inhibits the growth of triple-negative breast cancer cells but its lipophilicity restricts possible clinical application. This study therefore determined the feasibility of encapsulating piperine in nanoparticles (NPs) to increase its solubility in an aqueous environment. Materials and Methods: Piperine-loaded biodegradable methoxy poly(ethylene glycol)-poly(lactic-co-glycolic) acid copolymer-based NPs were produced by single emulsion solvent extraction and thin-film hydration. Growth and viability of triple-negative breast cancer (TNBC) cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Annexin-V-FLUOS/propidium iodide staining, respectively. Results: Thin-film hydration was superior to single emulsion solvent extraction, yielding piperine-loaded NPs with an average size of 50 nm. Piperine-loaded NPs inhibited TNBC cell growth and induced apoptosis while sparing normal fibroblasts. Conclusion: It is feasible to deliver a cytotoxic concentration of piperine to TNBC cells via NPs with the potential for improved bioavailability and solubility in biological fluids.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

mPEG-PLA from PolySciTech used in development of quantitative microscopy assay for particle circulation time

Thursday, February 6, 2020, 9:43 AM ET

One of the key parameters for nanoparticle-based drug delivery is how long the particles can remain in the blood-stream before being removed by the bodily systems. The time it takes for roughly half the particles to be cleared by the liver, kidneys, or other mechanisms is considered the particle half-life and is a critical parameter in defining appropriate dosages of the particle materials. Recently, Researchers at Yale University used mPEG-PLA (AK054) from PolySciTech (www.polyscitech.com) to create test nanoparticles for work on their development of a microscopic-based technique which can quickly and efficiently determine particle half-life. This research holds promise for further development of nanotherapy based medicines. Read more: Bracaglia, Laura G., Alexandra S. Piotrowski-Daspit, Chun-Yu Lin, Zoe M. Moscato, Yongheng Wang, Gregory T. Tietjen, and W. Mark Saltzman. "High-throughput quantitative microscopy-based half-life measurements of intravenously injected agents." Proceedings of the National Academy of Sciences (2020). https://www.pnas.org/content/early/2020/01/30/1915450117.short

“Accurate analysis of blood concentration and circulation half-life is an important consideration for any intravenously administered agent in preclinical development or for therapeutic application. However, the currently available tools to measure these parameters are laborious, expensive, and inefficient for handling multiple samples from complex multivariable experiments. Here we describe a robust high-throughput quantitative microscopy-based method to measure the blood concentration and circulation half-life of any fluorescently labeled agent using only a small (2 µL) amount of blood volume, enabling additional end-point measurements to be assessed in the same subject. To validate this method, we demonstrate its use to measure the circulation half-life in mice of two types of fluorescently labeled polymeric nanoparticles of different sizes and surface chemistries and of a much smaller fluorescently labeled monoclonal antibody. Furthermore, we demonstrate the improved accuracy of this method compared to previously described methods.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLA-PEG-PLA-Acrylate from PolySciTech used in development of antibody-targeted crosslinked nanoparticles for brain-cancer treatment

Monday, February 3, 2020, 1:29 PM ET

Polymer particles are often generated from hydrophobic materials and typically held together by simple physical entanglement of the polymer chains. However, polymer particles can also be generated by chemically crosslinking together hydrophilic materials. This is useful for work with delivery of delicate structures such as antibody/antibody fragments. Recently, researchers at UCLA and Peking Union Medical College use PLA-PEG-PLA-acrylate (AI102) from PolySciTech (www.polyscitech.com) to create chemically-crosslinked nanocapsules for delivery of RTX. This research holds promise for improved therapies against brain cancer. Read more: Meng, Qin, Lan Wang, Di Wu, Christopher K. Williams, Duo Xu, Emiko Kranz, Qi Guo et al. "Enhanced Delivery of Rituximab into Brain and Lymph Nodes using Timed-Release Nanocapsules in Non-human Primates." Frontiers in Immunology 10 (2019): 3132. https://www.frontiersin.org/articles/10.3389/fimmu.2019.03132/full

“Tumor metastasis into the central nervous system (CNS) and lymph nodes (LNs) is a major obstacle for effective therapies. Therapeutic monoclonal antibodies (mAb) have revolutionized tumor treatment; however, their efficacy for treating metastatic tumors-particularly, CNS and LN metastases-is poor due to inefficient penetration into the CNS and LNs following intravenous injection. We recently reported an effective delivery of mAb to the CNS by encapsulating the anti-CD20 mAb rituximab (RTX) within a thin shell of polymer that contains the analogs of choline and acetylcholine receptors. This encapsulated RTX, denoted as n-RTX, eliminated lymphoma cells systemically in a xenografted humanized mouse model using an immunodeficient mouse as a recipient of human hematopoietic stem/progenitor cells and fetal thymus more effectively than native RTX; importantly, n-RTX showed notable anti-tumor effect on CNS metastases which is unable to show by native RTX. As an important step toward future clinical translation of this technology, we further analyzed the properties of n-RTX in immunocompetent animals, rats, and non-human primates (NHPs). Our results show that a single intravenous injection of n-RTX resulted in 10-fold greater levels in the CNS and 2-3-fold greater levels in the LNs of RTX, respectively, than the injection of native RTX in both rats and NHPs. In addition, we demonstrate the enhanced delivery and efficient B-cell depletion in lymphoid organs of NHPs with n-RTX. Moreover, detailed hematological analysis and liver enzyme activity tests indicate n-RTX treatment is safe in NHPs. As this nanocapsule platform can be universally applied to other therapeutic mAbs, it holds great promise for extending mAb therapy to poorly accessible body compartments.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLGA from PolySciTech Used in Research on Reducing Toxic Side-effects to the Liver

Thursday, January 30, 2020, 4:28 PM ET

The liver is a critical organ in the human body which performs several important chemical functions. Many medicinal compounds can lead to damage in the liver which limits their use. Recently, researchers at University of North Carolina at Chapel Hill used PLGA (AP018) from PolySciTech (www.polyscitech.com) to develop nanoparticles and assay the protective capabilities of these nanoparticles to protect liver cells from hepatotoxic compounds. This research holds promise to enable further development of nanotherapeutics. Read more: Yang, Feifei, Yusra Medik, Liantao Li, Xi Tian, Dong Fu, Kim LR Brouwer, Kyle Wagner et al. "Nanoparticle Drug Delivery Can Reduce the Hepatotoxicity of Therapeutic Cargo." Small (2020): 1906360. https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.201906360

“Abstract: Hepatotoxicity is a key concern in the clinical translation of nanotherapeutics because preclinical studies have consistently shown that nanotherapeutics accumulates extensively in the liver. However, clinical‐stage nanotherapeutics have not shown increased hepatotoxicity. Factors that can contribute to the hepatotoxicity of nanotherapeutics beyond the intrinsic hepatotoxicity of nanoparticles (NPs) are poorly understood. Because of this knowledge gap, clinical translation efforts have avoided hepatotoxic molecules. By examining the hepatotoxicity of nanoformulations of known hepatotoxic compounds, it is demonstrated that nanotherapeutics are associated with lower hepatotoxicity than their small‐molecule counterparts. It is also found that the reduced hepatotoxicity is related to the uptake of nanotherapeutics by macrophages in the liver. These findings can facilitate further development and clinical translation of nanotherapeutics.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

Thermogels from PolySciTech used in research on 3D printing of hydrogel substrates

Friday, January 24, 2020, 10:31 AM ET

Conventional 3D printing relies on heating a plastic above its melting point and then extruding it onto a cooled platform. Conversely, 3D printing with a Thermogel requires placing a cooled Thermogel solution onto a heated plate to form the gel. Recently, researchers at Purdue University and Korea Institute of Industrial Technology used NIPAM-co-MMA (AO023) from PolySciTech (www.polyscitech.com) to create 3-D printable hydrogel matrix. This research holds promise to enable generation of drug delivery systems and tissue scaffolds for biomedical applications in the future. Read more: Cheng, Cih, Yoon Jae Moon, Samuel Haidong Kim, Yong-Cheol Jeong, Jun Young Hwang, George T-C. Chiu, and Bumsoo Han. "Water-matrix interaction at the drop-drop interface during drop-on-demand printing of hydrogels." International Journal of Heat and Mass Transfer 150 (2020): 119327. https://www.sciencedirect.com/science/article/pii/S0017931019342085

“Highlights: Drop-drop interactions during hydrogel printing are explained considering water-matrix interactions within hydrogel drops printed. A similarity mechanism of water-matrix interaction, and associated dimensionless parameter are proposed. The water-matrix interactions at the drop-drop interfance affect the microstructure of hydrogel drops printed. Abstract: Hydrogel-based soft materials have been used in numerous applications in healthcare, food, pharmaceutical, and cosmetic industries. Manufacturing hydrogels whose functional properties and compositions are voxelized at superior spatial resolutions can significantly improve current applications as well as will enable a new generation of soft materials. However, it remains challenging to control the structure and composition of soft materials reliably. In this context, the drop-on-demand (DOD) printing of hydrogels shows excellent potential to address this manufacturing challenge. Despite this potential, a lack of mechanistic understanding of the behavior of printed hydrogel drops makes it challenging to design and optimize DOD printing protocols for a wide variety of hydrogels. In particular, the curing of hydrogel drops, which requires dehydration of printed hydrogel drops, is poorly understood. In this study, thus, a hypothesis was postulated and tested that water-matrix interaction at drop-drop interfaces during curing processes determine the quality of hydrogels printed. Both computational and experimental studies were performed to establish a mechanism of the water-matrix interaction within printed hydrogel drops. The results were further discussed to establish a dimensionless similarity parameter that can characterize water transports during the hydrogel dehydration process. Keywords: Water transport Evaporation Interstitial water Poroelastic material 3D printing”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLGA from PolySciTech used in development of nanoparticle delivery system for CRISPR–Cas9 plasmid

Friday, January 24, 2020, 10:30 AM ET

Although gene-editing has been promoted as a potential usage of CRISPR technology there remains a lack of method to deliver the components for this to the intraceullular area. Recently, researchers at Virginia Tech used PLGA (AP063) and PLGA-NH2 (AI063) from PolySciTech (www.polyscitech.com) to create plasmid-encapsulated nanoparticles and measured the release from these as part of a DNA delivery system. This research holds promise to unlock the potential of CRISPR by allowing the DNA systems to be uptaken into target cells. Read more: Jo, Ami, Veronica M. Ringel-Scaia, Dylan K. McDaniel, Cassidy A. Thomas, Rui Zhang, Judy S. Riffle, Irving C. Allen, and Richey M. Davis. "Fabrication and characterization of PLGA nanoparticles encapsulating large CRISPR–Cas9 plasmid." Journal of Nanobiotechnology 18, no. 1 (2020): 16. https://link.springer.com/article/10.1186/s12951-019-0564-1

“Background: The clustered regularly interspaced short palindromic repeats (CRISPR) and Cas9 protein system is a revolutionary tool for gene therapy. Despite promising reports of the utility of CRISPR–Cas9 for in vivo gene editing, a principal problem in implementing this new process is delivery of high molecular weight DNA into cells. Results: Using poly(lactic-co-glycolic acid) (PLGA), a nanoparticle carrier was designed to deliver a model CRISPR–Cas9 plasmid into primary bone marrow derived macrophages. The engineered PLGA-based carriers were approximately 160 nm and fluorescently labeled by encapsulation of the fluorophore 6,13-bis(triisopropylsilylethynyl) pentacene (TIPS pentacene). An amine-end capped PLGA encapsulated 1.6 wt% DNA, with an encapsulation efficiency of 80%. Release studies revealed that most of the DNA was released within the first 24 h and corresponded to ~ 2–3 plasmid copies released per nanoparticle. In vitro experiments conducted with murine bone marrow derived macrophages demonstrated that after 24 h of treatment with the PLGA-encapsulated CRISPR plasmids, the majority of cells were positive for TIPS pentacene and the protein Cas9 was detectable within the cells. Conclusions: In this work, plasmids for the CRISPR–Cas9 system were encapsulated in nanoparticles comprised of PLGA and were shown to induce expression of bacterial Cas9 in murine bone marrow derived macrophages in vitro. These results suggest that this nanoparticle-based plasmid delivery method can be effective for future in vivo applications of the CRISPR–Cas9 system. Keywords: Nanoprecipitation Transfection CRISPR–Cas9 PLGA nanoparticles”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLGA from PolySciTech used in comparative assay of nanoparticle delivery and drug release

Friday, January 24, 2020, 10:16 AM ET

The pathway to generating drug-delivery technologies to treat cancer is not necessarily linear as the process is complex. Notably, the motion of the nanoparticles does not always correlate to successful delivery of drug to the tumor. Recently, researchers at Seoul National University, Catholic University of Korea (Korea), and Purdue University used PLGA (AP020) from PolySciTech (www.polyscitech.com) to create quinic-acid decorated nanoparticles. They found that the motion of the particles did not correlate to efficacy, however, indicating that the release of carfizomib is the limiting step for efficacy. Read more: Jun, Yearin, Jun Xu, Hyungjun Kim, Ji Eun Park, Yoo-Seong Jeong, Jee Sun Min, Naeun Yoon et al. "Carfilzomib delivery by quinic acid-conjugated nanoparticles: Discrepancy between tumoral drug accumulation and anticancer efficacy in a murine 4T1 orthotopic breast cancer model." Journal of Pharmaceutical Sciences (2020). https://www.sciencedirect.com/science/article/pii/S0022354920300137

“Abstract: Despite being a major breakthrough in multiple myeloma therapy, carfilzomib (CFZ, a second-generation proteasome inhibitor drug) has been largely ineffective against solid cancer, possibly due to its pharmacokinetic drawbacks including metabolic instability. Recently, quinic acid (QA, a low-affinity ligand of selectins upregulated in peritumoral vasculature) was successfully utilized as a surface modifier for nanoparticles containing paclitaxel. Here, we designed QA-conjugated nanoparticles containing CFZ (CFZ@QANP; the surface of poly(lactic-co-glycolic acid) (PLGA) nanoparticles modified by conjugation with a QA derivative). Compared to the clinically used cyclodextrin-based formulation (CFZ-CD), CFZ@QANP enhanced the metabolic stability and in vivo exposure of CFZ in mice. CFZ@QANP however showed little improvement in suppressing tumor growth over CFZ-CD against the murine 4T1 orthotopic breast cancer model. CFZ@QANP yielded no enhancement in proteasomal inhibition in excised tumors despite having a higher level of remaining CFZ than CFZ-CD. These results likely arise from delayed, incomplete CFZ release from CFZ@QANP as observed using biorelevant media in vitro. These results suggest that the applicability of QANP may not be predicted by physicochemical parameters commonly used for formulation design. Our current results highlight the importance of considering drug release kinetics in designing effective CFZ formulations for solid cancer therapy. Keywords: Proteasome inhibitor carfilzomib nanoparticle quinic acid”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLA from PolySciTech used in development of Rivastigmine-based therapy for Alzheimer’s disease

Tuesday, January 21, 2020, 4:33 PM ET

Alzheimer’s disease is a progressive neurodegenerative disease which has few treatment options. Recently, Researchers at North Dakota State University used PLA (AP047) from PolySciTech (www.polyscitech.com) as part of developing a depot formulation for treatment of alzeheimers disease. This research holds promise to provide enhanced therapies against alzeheimer’s disease. Read more: Lipp, Lindsey, Divya Sharma, Amrita Banerjee, and Jagdish Singh. "In Vitro and in Vivo Optimization of Phase Sensitive Smart Polymer for Controlled Delivery of Rivastigmine for Treatment of Alzheimer’s Disease." Pharmaceutical Research 37, no. 3 (2020): 34. https://link.springer.com/article/10.1007/s11095-020-2757-6

“Abstract: Purpose: Alzheimer’s disease is a neurodegenerative disorder, and most common form of dementia afflicting over 35 million people worldwide. Rivastigmine is a widely used therapeutic for ameliorating clinical manifestations of Alzheimer’s disease. However, current treatments require frequent dosing either orally or via transdermal patch that lead to compliance issues and administration errors risking serious adverse effects. Our objective was to develop a smart polymer based delivery system for controlled release of rivastigmine over an extended period following a single subcutaneous injection. Methods: Rivastigmine release was optimized by tailoring critical factors including polymer concentration, polymer composition, drug concentration, solvent composition, and drug hydrophobicity (rivastigmine tartrate vs base). Optimized in vitro formulation was evaluated in vivo for safety and efficacy. Results: Formulation prepared using PLGA (50:50) at 5% w/v in 95:5 benzyl benzoate: benzoic acid demonstrated desirable controlled drug release characteristics in vitro. The formulation demonstrated sustained release of rivastigmine tartrate for 7 days in vivo with promising biocompatibility and acetylcholinesterase inhibition efficacy for 14 days. Conclusion: The results exemplify an easily injectable controlled release formulation of rivastigmine prepared using phase-sensitive smart polymer. The optimized formulation significantly increases the dosing interval, and can potentially improve patient compliance as well as quality of life of patients living with Alzheimer’s disease. Key Words: alzheimer’s disease controlled release phase sensitive rivastigmine smart polymers”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLGA-PEG-Mal from PolySciTech used in development of breast-cancer targeting nanoparticle system.

Tuesday, January 21, 2020, 4:33 PM ET

Despite advances in therapies certain types of breast cancers known as triple-negative breast cancers remain difficult to treat due to their invasive nature and lack of specific target. Recently, researchers at University of Maryland, Translational Genomics Research Institute, and Mayo Clinic Arizona used PLGA-PEG-maleimide (AI053), mPEG-PLGA (AK010), and PLGA-rhodamine (AV011) from PolySciTech (www.polyscitech.com) to develop a series of targeted nanoparticles and tested these for efficacy against triple-negative breast cancer. This research holds promise to improve therapies against breast and other cancers. Read more: Dancy, Jimena G., Aniket S. Wadajkar, Nina P. Connolly, Rebeca Galisteo, Heather M. Ames, Sen Peng, Nhan L. Tran et al. "Decreased nonspecific adhesivity, receptor-targeted therapeutic nanoparticles for primary and metastatic breast cancer." Science Advances 6, no. 3 (2020): eaax3931. https://advances.sciencemag.org/content/advances/6/3/eaax3931.full.pdf

“Abstract: Development of effective tumor cell–targeted nanodrug formulations has been quite challenging, as many nanocarriers and targeting moieties exhibit nonspecific binding to cellular, extracellular, and intravascular components. We have developed a therapeutic nanoparticle formulation approach that balances cell surface receptor-specific binding affinity while maintaining minimal interactions with blood and tumor tissue components (termed “DART” nanoparticles), thereby improving blood circulation time, biodistribution, and tumor cell–specific uptake. Here, we report that paclitaxel (PTX)–DART nanoparticles directed to the cell surface receptor fibroblast growth factor–inducible 14 (Fn14) outperformed both the corresponding PTX-loaded, nontargeted nanoparticles and Abraxane, an FDA-approved PTX nanoformulation, in both a primary triple-negative breast cancer (TNBC) model and an intracranial model reflecting TNBC growth following metastatic dissemination to the brain. These results provide new insights into methods for effective development of therapeutic nanoparticles as well as support the continued development of the DART platform for primary and metastatic tumors.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLGA from PolySciTech used in development of 3D-printable Bioink for biomedical applications

Tuesday, January 21, 2020, 4:32 PM ET

3D Printing is a powerful technique which enables generation of unique structures that can be widely applied to biomedical applications. Recently, researchers from University of Prince Edward Island (Canada) used PLGAs (AP149, AP136, AP020, and AP021) from PolySciTech (www.polyscitech.com) to develop a series of 3D printable constructs. This research holds promise to provide improved drug-eluting implants and scaffolds. Read more: Naseri, Emad, Haley Butler, Wyatt MacNevin, Marya Ahmed, and Ali Ahmadi. "Low-temperature solvent-based 3D printing of PLGA: a parametric printability study." Drug Development and Industrial Pharmacy just-accepted (2020): 1-13. https://www.tandfonline.com/doi/abs/10.1080/03639045.2019.1711389

“Abstract: In this paper, a novel low-temperature 3D printing technique is introduced and characterized through a parametric printability study to fabricate poly-lactic-co-glycolic acid (PLGA) constructs using methyl ethyl ketone (MEK) as a solvent. The effects of varying concentrations of PLGA in MEK solvent, lactic to glycolic ratio of PLGA, the molecular weight of PLGA, and the scaling of PLGA constructs on the printability are investigated. PLGA concentrations of higher than 80% w/v, lactic to glycolic ratio more than 75%, molecular weight more than 100 kDa, and printing through nozzles smaller than 0.96 mm internal diameter are recommended for 3D printing of PLGA constructs with high shape fidelity. Ultimately, a vacuum drying solvent removal process is implemented, and Proton Nuclear Magnetic Resonance (1H-NMR) spectroscopy is used to confirm complete removal of the solvent from PLGA constructs. The results of this study can be used for the development of drug-eluting implants. Keywords: 3D printing, PLGA, Printability, Drug Eluting Implants, Bioabsorbable Scaffolds”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

Polymer University 107: Unboxing AK149

Friday, January 17, 2020, 1:44 PM ET

Tech video featuring methoxy poly(ethylene glycol)-b-poly(DL)lactide copolymer and its use in formulating nanoparticles for poorly soluble drug delivery. Humorously presented in the format of a classic 'unboxing video.'

PLCL from PolySciTech used in development of vascular grafts.

Tuesday, January 14, 2020, 11:04 AM ET

All parts of the body require continuous exposure to oxygenated blood to stay alive. Damage to vascular systems can occur from a variety of causes (cholesterol blockage, wall-thinning/rupture, trauma, etc.) and in these situations the blood vessels may need surgically repaired to maintain blood flow to critical regions. Recently, researchers at Nanyang Technological University (Singapore) and Technion–Israel Institute of Technology (Israel) used PLCL (AP124, AP145) from PolySciTech (www.polyscitech.com) to create prototype vascular grafts. This research holds promise to improve vascular grafting as a treatment option for damaged blood vessels. Read more: Behr, Jean‐Marc, Scott Alexander Irvine, Chaw‐Su Thwin, Ankur Harish Shah, Min‐Chul Kraun Bae, Eyal Zussman, and Subbu Venkatraman. "Matching Static and Dynamic Compliance of Small‐Diameter Arteries, with Poly (lactide‐co‐caprolactone) Copolymers: In Vitro and In Vivo Studies." Macromolecular Bioscience (2020): 1900234. https://onlinelibrary.wiley.com/doi/abs/10.1002/mabi.201900234

“Abstract: Mechanical mismatch between vascular grafts and blood vessels is a major cause of smaller diameter vascular graft failure. To minimize this mismatch, several poly‐l‐lactide‐co‐ε‐caprolactone (PLC) copolymers are evaluated as candidate materials to fabricate a small diameter graft. Using these materials, tubular prostheses of 4 mm inner diameter are fabricated by dip‐coating. In vitro static and dynamic compliance tests are conducted, using custom‐built apparatus featuring a closed flow system with water at 37 °C. Grafts of PLC monomer ratio of 50:50 are the most compliant (1.56% ± 0.31∙mm Hg−2), close to that of porcine aortic branch arteries (1.56% ± 0.43∙mm Hg−2), but underwent high continuous dilatation (87 µm min−1). Better matching is achieved by optimizing the thickness of a tubular conduit made from 70:30 PLC grafts. In vivo implantation and function of a PLC 70:30 conduit of 150 µm wall‐thickness (WT) are tested as a rabbit aorta bypass. An implanted 150 µm WT PLC 70:30 prosthesis is observed over 3 h. The recorded angiogram shows continuous blood flow, no aneurysmal dilatation, leaks, or acute thrombosis during the in vivo test, indicating the potential for clinical applications.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLLA from PolySciTech used in research on controlling immune-response to implant surfaces

Tuesday, January 14, 2020, 11:03 AM ET

In many ways, the human immune system can be considered to be similar to a viscous dog on a chain. It will attack anything that gets within reach that it does not recognize as part of its owner or self. This is great when it comes to bacterial and viral infections which legitimately need to be attacked to prevent infection. This is not great when it comes to medical implants and other materials which may evoke an inflammatory response. Recently, researchers at The Heart Research Institute (Sydney, Australia) University of Sydney (Australia), Shanghai Tongji University, and Shanghai Jiaotong University School of Medicine (China) used PLLA (AP006) from PolySciTech (www.polyscitech.com) to create electrospun meshes of this polymer. They treated these meshes with M-CSF and tested the ability of this treatment to reduce the inflammation response. This research holds promise to improve the functionality of implant materials by reducing the body’s immune response against it. Read more: Yang, Nianji, Richard P. Tan, Alex HP Chan, Bob SL Lee, Miguel Santos, Juichien Hung, Yun Liao et al. "Immobilised Macrophage Colony-Stimulating Factor (M-CSF) regulates the foreign body response to implanted materials." ACS Biomaterials Science & Engineering (2020). https://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.9b01887

“Abstract: The functionality and durability of implanted biomaterials are often compromised by an exaggerated foreign body reaction (FBR). M1/M2 polarization of macrophages is a critical regulator of scaffold-induced FBR. Macrophage colony-stimulating factor (M-CSF), a hematopoietic growth factor, induces macrophages into an M2-like polarized state, leading to immunoregulation and promoting tissue repair. In the present study, we explored the immunomodulatory effects of surface bound M-CSF on poly-l-lactic acid (PLLA)-induced FBR. M-CSF was immobilized on the surface of PLLA via plasma immersion ion implantation (PIII). M-CSF functionalized PLLA, PLLA-only, and PLLA+PIII were assessed in an IL-1β luciferase reporter mouse to detect real-time levels of IL-1β expression, reflecting acute inflammation in vivo. Additionally, these different treated scaffolds were implanted subcutaneously into wild-type mice to explore the effect of M-CSF in polarization of M2-like macrophages (CD68+/CD206+), related cytokines (pro-inflammatory: IL-1β, TNF and MCP-1; anti-inflammatory: IL-10 and TGF-β), and angiogenesis (CD31) by immunofluorescent staining. Our data demonstrated that IL-1β activity in M-CSF functionalized scaffolds was ∼50% reduced compared to PLLA-only at day 1 (p < 0.01) and day 2 (p < 0.05) post-implantation. There were >2.6-fold more CD206+ macrophages in M-CSF functionalized PLLA compared to PLLA-only at day 7 (p < 0.001), along with higher levels of IL-10 at both day 7 (p < 0.05) and day 14 (p < 0.01), and TGF-β at day 3 (p < 0.05), day 7 (p < 0.05), and day 14 (p < 0.001). Lower levels of pro-inflammatory cytokines were also detected in M-CSF functionalized PLLA in the early phase of the immune response compared to PLLA-only: a ∼58% decrease at day 3 in IL-1β; a ∼91% decrease at day 3 and a ∼66% decrease at day 7 in TNF; and a ∼60% decrease at day 7 in MCP-1. Moreover, enhanced angiogenesis inside and on/near the scaffold was observed in M-CSF functionalized PLLA compared to PLLA-only at day 3 (p < 0.05) and day 7 (p < 0.05), respectively. Overall, M-CSF functionalized PLLA enhanced CD206+ macrophage polarization and angiogenesis, consistent with lower levels of pro-inflammatory cytokines and higher levels of anti-inflammatory cytokines in early stages of the host response, indicating potential immunoregulatory functions on the local environment.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLGA from PolySciTech used in development of Quinacrine-loaded PLGA nanoparticles for treatment of lung-cancer

Tuesday, January 14, 2020, 11:02 AM ET

A relatively untapped source of novel therapeutic compounds is the reapplication of existing drugs for new purposes. Doing this requires novel applications and delivery systems. Quinacrine, traditionally an antimalarial drug, has shown promise as an anticancer agent under the right conditions. Recently, researchers at Harvard University, Keck Graduate Institute, St. John’s University, and University of La Verne used PLGA (AP082) from PolySciTech (www.polyscitech.com) to create Quinacrine-loaded PLGA nanoparticles for treatment of lung-cancer. This research holds promise to provide for improved therapies against lung-cancer. Read more: Vaidya, Bhuvaneshwar, Nishant S. Kulkarni, Snehal K. Shukla, Vineela Parvathaneni, Gautam Chauhan, Jenna K. Damon, Apoorva Sarode et al. "Development of Inhalable Quinacrine Loaded Bovine Serum Albumin Modified Cationic Nanoparticles: Repurposing Quinacrine for Lung Cancer Therapeutics." International Journal of Pharmaceutics (2020): 118995. https://www.sciencedirect.com/science/article/pii/S0378517319310567

“Abstract: Drug repurposing is on the rise as an atypical strategy for discovery of new molecules, involving use of pre-existing molecules for a different therapeutic application than the approved indication. Using this strategy, the current study aims to leverage effects of quinacrine (QA), a well-known anti-malarial drug, for treatment of non-small cell lung cancer (NSCLC). For respiratory diseases, designing a QA loaded inhalable delivery system has multiple advantages over invasive delivery. QA-loaded nanoparticles (NPs) were thus prepared using polyethyleneimine (PEI) as a cationic stabilizer. While the use of PEI provided cationic charge on the particles, it also mediated a burst release of QA and demonstrated potential particle toxicity. These concerns were circumvented by coating nanoparticles with bovine serum albumin (BSA), which retained the cationic charge, reduced NP toxicity and modulated QA release. Prepared nanoparticles were characterized for physicochemical properties along with their aerosolization potential. Therapeutic efficacy of the formulations was tested in different NSCLC cells. Mechanism of higher anti-proliferation was evaluated by studying cell cycle profile, apoptosis and molecular markers involved in the progression of lung cancer. BSA coated QA nanoparticles demonstrated good aerosolization potential with a mass median aerodynamic diameter of significantly less than 5µm. Nanoparticles also demonstrated improved therapeutic efficacy against NSCLC cells in terms of low IC50 values, cell cycle arrest at G2/M phase and autophagy inhibition leading to increased apoptosis. BSA coated QA NPs also demonstrated enhanced therapeutic efficacy in a 3D cell culture model. The present study thus lays solid groundwork for pre-clinical and eventual clinical studies as a standalone therapy and in combination with existing chemotherapeutics.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLGA from PolySciTech used in development of Intra-ductal delivery system for Breast Cancer Therapy

Wednesday, January 8, 2020, 2:22 PM ET

Treating cancer by chemotherapy and other therapeutic means requires maintaining a very high drug concentration at the tumor site and minimizing the drug concentration in other parts of the body where it can cause side effects. For breast cancers, the mammary ducts provide regions where doses could potentially be administered however keeping the dose in that location without flowing to other parts of the body remains a challenge. Recently, researchers at South Dakota State University used PLGA (AP211, AP252, AP062) from PolySciTech (www.polyscitech.com) to develop microparticle and in-situ gel formulations for nanoparticle delivery into the mammary ducts. This research holds promise to improve breast cancer therapies in the future. Read more: Joseph, Mibin Kuruvilla, Md Saiful Islam, Joshua Reineke, Michael Hildreth, Tofuko Woyengo, Angela Pillatzki, Aravind Baride, and Omathanu Perumal. "Intraductal Drug Delivery to the Breast: Effect of Particle size and Formulation on Breast Duct and Lymph Node Retention." Molecular Pharmaceutics (2019). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.9b00879

“Abstract: Drug delivery by direct intraductal administration can achieve high local drug concentration in the breast and minimize systemic levels. However, the clinical application of this approach for breast cancer treatment is limited by the rapid clearance of the drug from the ducts. With the goal of developing strategies to prolong drug retention in the breast, this study was focused on understanding the influence of particle size and formulation on breast duct and lymph node retention. Fluorescent labeled polystyrene (PS) particles ranging in size from 100-1000 nm were used to study the influence of particle size. Polylactic acid-co-glycolic acid (PLGA) was used to develop and test formulations for intraductal delivery. Cy5.5, a near IR dye was encapsulated in PLGA microparticles, nanoparticles and in-situ gel to study the biodistribution in rats using an in-vivo imager. PS microparticles (1 µm) showed longer retention in the duct compared to 100 and 500 nm nanoparticles. The ductal retention half-life was five-fold higher for PS microparticles compared to the nanoparticles. On the other hand, the free dye was cleared from the breast within 6 hours. PLGA nanoparticles sustained the release of Cy 5.5 for >4 days. Microparticles and gel showed a much slower release than nanoparticles. PLGA in-situ gel and microparticles were retained in the breast for up to 4 days, while the nanoparticles were retained in the breast for 2 days. PLGA nanoparticles and microparticles drained to the axillary lymph node and were retained for up to 24 hours and 48 hours respectively, while the in-situ gel and free dye did not show any detectable fluorescence in the lymph nodes. Taken together, the results demonstrate the feasibility of prolonged retention in the breast duct and lymph node by optimal formulation design. The findings can serve as a framework to design formulations for localized treatment of breast cancer.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

mPEG-PLA and mPEG-PCL from PolyScitech used in research on micelle stability in biological fluids

Thursday, January 2, 2020, 3:52 PM ET

Polymer micelles for drug delivery are typically comprised of hydrophobic (typically a polyester) and hydrophilic (typically PEG) arms on a block copolymer. Based on the polymer as well as the formulation approaches the resultant micelle can have a wide range of properties including size, zeta potential, etc. Although often tested in either plain water or saline, it is important to understand the behavior of these formulations in biological fluids where they will ultimately need to be in order to be used in drug-delivery applications. Recently, researchers at University of Illinois at Chicago used mPEG-PCL (Polyvivo AK073), and mPEG-PLA (AK009, AK054) from PolySciTech (www.polyscitech.com) to test polymer micelle stability in a series of biological fluids. This research holds promise for improved development of micelles for drug-delivery applications. Read more: Langridge, Timothy D., and Richard A. Gemeinhart. "Toward understanding polymer micelle stability: Density ultracentrifugation offers insight into polymer micelle stability in human fluids." Journal of Controlled Release (2019). https://www.sciencedirect.com/science/article/pii/S0168365919307576

“Abstract: Micelles, as a class of drug delivery systems, are underrepresented among United States Food and Drug Administration approved drugs. A lack of clinical translation of these systems may be due to, in part, to a lack of understanding of micelle interactions with biologic fluids following injection. Despite the limited clinical translation, micelles remain an active area of research focus and pre-clinical development. The goal of the present study was to examine the stability of amphiphilic block copolymer micelles in biologic fluids to identify the properties and components of biologic fluids that influence micelle stability. Micelle stability, measured via Förster resonance energy transfer-based fluorescent spectrometry, was complemented with density ultracentrifugation to reveal the colocalized, or dissociated, state of the dye cargo after exposure to human biologic fluids. Polymeric micelles composed of poly(ethylene glycol-block-caprolactone) (mPEG-CL) and poly(ethylene glycol-block-lactide) (mPEG-LA) were unstable in fetal bovine serum, human serum and synovial fluid, with varying levels of instability observed in ascites and pleural fluid. All polymeric micelles exhibited stability in cerebrospinal fluid, highlighting the potential for local cerebro-spinal administration of micelles. Interestingly, mPEG2.2k-CL3.1k and mPEG2k-LA2.7k micelles favored dissolution whereas mPEG5.4k-LA28.5k micelles favored stability. Taken together, our data offers both quantitative and qualitative evidence for micelle stability within human biologic fluids and offers evidence of polymer micelle instability in biologic fluids that is not explained by either total protein content or total unsaturated lipid content. The results help to identify potential sites for local delivery where stability is maintained. Highlights: Human serum is one of the most destabilizing biologic fluids for polymer micelles. Polymer micelles appear stable in human cerebrospinal fluid. Biologic fluid total protein & lipid do not correlate with micelle instability. Typical micelle parameters do not correlate with destabilization in biologic fluids. Gradient ultracentrifugation complements other micelle characterization methods. Keywords: Micelle Stability Gradient ultracentrifugation Critical micelle concentration Human fluid”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/)

PLGA from PolySciTech used in development of antibiotic-releasing films from sinus stent

Thursday, January 2, 2020, 3:51 PM ET

Chronic sinus infection can occur from antibiotic-resistant forms of pseudomonas bacteria. One means to hold the sinus open is to place a stent however further healing can be accomplished by having a drug-eluting layer on the stent release medicines into the surrounding tissue. Recently, researchers at The University of Alabama at Birmingham utilized PLGA from PolySciTech (www.polyscitech.com) as part of their development of a drug-eluting sinus stent. This research holds promise to improve therapies against antibiotic-resistant strains of bacteria that can lead to sinus issues. Read more: Lim, Dong‐Jin, Justin McCormick, Daniel Skinner, Shaoyan Zhang, Jeffrey B. Elder, John G. McLemore, Mark Allen et al. "Controlled delivery of ciprofloxacin and ivacaftor via sinus stent in a preclinical model of Pseudomonas sinusitis." In International Forum of Allergy & Rhinology. John Wiley & Sons, Ltd, 2019. https://onlinelibrary.wiley.com/doi/abs/10.1002/alr.22514

“Abstract: Background: Pseudomonas aeruginosa is common in chronic rhinosinusitus (CRS) and frequently resistant to antibiotic treatment. We recently described the ciprofloxacin and ivacaftor‒releasing biodegradable sinus stent (CISS)―a drug‐delivery system that administers ciprofloxacin and the mucociliary activator (ivacaftor) at high local concentrations with prolonged mucosal contact time and sustained delivery. The objective of this study is to evaluate the efficacy of the CISS in a rabbit model of P aeruginosa (PAO1 strain) sinusitis. Methods: Ciprofloxacin/ivacaftor (double layer) was coated on biodegradable poly‐D/L‐lactic acid (PLLA). A total of 10 sinus stents (5 bare PLLA stent controls, 5 CISSs) were placed unilaterally in rabbit maxillary sinuses via dorsal sinusotomy after inducing infection for 1 week with PAO1. Animals were assessed 3 weeks after stent insertion with sinus culture, nasal endoscopy, computed tomography scan, histopathology, and in‐vivo sinus potential difference (SPD) assay. Results: Rabbits treated with CISS had significant reductions in computed tomography (∆ Kerschner scale: control, 0.55 ± 0.92; CISS, −5.92 ± 1.69; p = 0.024) and endoscopy (control, 4.0 ± 0.0; CISS, 1.875 ± 0.74; p = 0.003) scores. A 2‐log reduction of PAO1 was observed (control, −2.14 ± 0.77; CISS, 1.84 ± 1.52; p = 0.047). SPD revealed significantly increased Cl− transport in the CISS group compared with the control group (Cl−‐free + forskolin ΔPD: control, −4.23 ± 1.04 mV; CISS, −18.36 ± 6.31 mV; p = 0.026). Finally, marked improvements were noted in the histology of the mucosa and submucosa in treated animals. Conclusion: The CISS had robust clinical efficacy in treating P aeruginosa rabbit sinusitis. The innovative design of double‐layered drug coating on the surface of the biodegradable stent may provide therapeutic advantages over current treatment strategies for P aeruginosa sinusitis.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLGA from PolySciTech used in development of novel tissue adhesive formulation

Thursday, January 2, 2020, 3:50 PM ET

During surgery and for healing of traumatic injuries it is often necessary to use bioadhesives to close wounds and hold tissues together. Such adhesives must have good adhesion to wet tissue (underlying skin, muscle, fat, etc.) as well as good biocompatibility/biodegradation to allow for subsequent healing of the joined tissues. Recently, researchers at The Pennsylvania State University, Harvard Medical School, (USA) Harbin Engineering University, Chengdu University, Southern Medical University, and Jilin Medical University (China) used PLGA (PolyVivo AP154) from PolySciTech (www.polyscitech.com) as a control article in their development of a citrate-based adhesive. This research holds promise to lead to improvements in tissue adhesives for surgical and regenerative medicine applications. Read more: Lu, Xili, Sanjun Shi, Hanmei Li, Ethan Gerhard, Zhihui Lu, Xinyu Tan, Wenliang Li et al. "Magnesium oxide-crosslinked low-swelling citrate-based mussel-inspired tissue adhesives." Biomaterials (2019): 119719. https://www.sciencedirect.com/science/article/pii/S0142961219308373

“Abstract: Tissue adhesives are commonly used in surgeries and regenerative engineering for the repair and regeneration of topical and internal wounds on tissues and organs such as skin, heart, blood vessels, and bone. However, achieving rapid crosslinking, strong wet adhesion and cohesion strengths, and minimal cytotoxicity remains a critical roadblock for clinical translation. Herein, in contrast to harsh and cytotoxic oxidants, magnesium oxide (MgO) particles were found to facilitate rapid crosslinking for injectable citrate-based mussel-inspired tissue bioadhesives synthesized by reacting citric acid, PEG-PPG-PEG diol and dopamine (iC-EPE). Our results confirmed the role of MgO particles as both crosslinkers and composite fillers to concurrently enhance bioadhesive cohesion and adhesion. iC-EPE crosslinked by MgO with/without sodium periodate (PI) exhibit enhanced mechanical strengths (1.0 Mpa < tensile strength ≤ 4.5 MPa) compared to that of iC-EPE crosslinked only by PI (~0.75 MPa), high adhesion strength (up to 125 kPa, 8 fold that of fibrin glue (~15 kPa)), tunable degradability (full degradation from <1 to="" week=""> 1 month), excellent in vitro and in vivo biocompatibility, encouraging anti-bacterial performance, and favorable wound closure efficacy. Thus, MgO crosslinked bioadhesives possess great potential for a wide range of applications in surgery and regenerative engineering. Keywords: Magnesium oxide (MgO), Mussel-inspired adhesion, Citrate, Tissue adhesives, Wound closure”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

mPEG-PLA from PolySciTech used in the development of a Vessel-Perfusion system to better track nanoparticle motility and uptake

Monday, December 23, 2019, 3:20 PM ET

A classic problem with medicine is that the administered dose has poor uptake or targeting which reduces the efficacy of the drug. Having a better understanding for how drug loaded in nanoparticles move and are uptaken in blood vessels will enable the development of improved targeted therapies. Recently, researchers at Yale University used mPEG-PLA (Polyvivo AK054) from PolySciTech (www.polyscitech.com) as part of evaluating their developed perfusion testing chamber. This research holds promise to lead to improved nanotherapeutics in the future. Read more: Lysyy, Taras, Laura G. Bracaglia, Lingfeng Qin, Claire Albert, Jordan S. Pober, George Tellides, W. Mark Saltzman, and Gregory T. Tietjen. "Ex vivo isolated human vessel perfusion system for the design and assessment of nanomedicines targeted to the endothelium." Bioengineering & Translational Medicine. https://aiche.onlinelibrary.wiley.com/doi/abs/10.1002/btm2.10154

“Abstract: Endothelial cells play a central role in the process of inflammation. Their biologic relevance, as well as their accessibility to IV injected therapeutics, make them a strong candidate for treatment with molecularly‐targeted nanomedicines. Typically, the properties of targeted nanomedicines are first optimized in vitro in cell culture and then in vivo in rodent models. While cultured cells are readily available for study, results obtained from isolated cells can lack relevance to more complex in vivo environments. On the other hand, the quantitative assays needed to determine the impact of NP design on targeting efficacy are difficult to perform in animal models. Moreover, results from animal models often translate poorly to human systems. To address the need for an improved testing platform, we developed an Isolated Vessel Perfusion System (IVPS) to enable dynamic and quantitative study of vascular‐targeted nanomedicines in readily obtainable human vessels isolated from umbilical cords or placenta. We show that this platform technology enables the evaluation of parameters that are critical to targeting efficacy (including flow rate, selection of targeting molecule, and temperature). Furthermore, biologic replicates can be easily produced by evaluating multiple vessel segments from the same human donor in independent, modular chambers. The chambers can also be adapted to house vessels of a variety of sizes, enabling subsequent study of vessel segments in vivo following transplantation into immunodeficient mice. We believe this perfusion system can help to address long‐standing issues in endothelial targeted nanomedicines and thereby enable more effective clinical translation.”

- Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

- Notice: Akina, Inc. will be closed December 24th through January 1st for the holidays. Orders placed during this time will be processed when we re-open on Thursday, January 2, 2020.

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.34309196472168 seconds)


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