Friday, January 18, 2019

PLGA from PolySciTech used in study on nanoparticle/microparticle interactions with immune cells


The human immune system does a spectacular job at attacking and destroying anything which is deemed (from a biochemical standpoint) to be ‘non-self’ in nature. In the case of bacterial or viral infection, this is quite a useful and necessary feature which enables humans to survive these infections. In drug delivery applications, however, it presents a problem as particles loaded with medicines intended for delivery of the therapeutic molecule can be attacked by phagocytes (i.e. white blood cells) and destroyed. Recently, researchers at The Indian Institute of Science used PLGA (AP154) from PolySciTech (www.polyscitech.com) to develop nanoparticles and track their cellular interactions. This research holds promise for better understanding of nanoparticle/microparticle circulation and clearance as it applies to drug delivery. Read more: Sharma, Preeti, Devashish Sen, Varsha Neelakantan, Vinidhra Shankar, and Siddharth Jhunjhunwala. "Disparate effects of PEG or albumin based surface modification on uptake of nano-and micro-particles." Biomaterials Science (2019). https://pubs.rsc.org/en/content/articlelanding/2019/bm/c8bm01545g

“Abstract: Surface modification of particulate systems is a commonly employed strategy to alter their interaction with proteins and cells. Past studies on nano-particles have shown that surface functionalization with polyethylene glycol (PEG) or proteins such as albumin increases circulation times by reducing their phagocytic uptake. However, studies on surface functionalized micro-particles have reported contradictory results. Here, we investigate the effects of surface functionalization using polystyrene particles with 4 different diameters ranging from 30 nm-2.6 µm and coating them either with albumin or PEG. Our results show that with increasing particle size, surface functionalization has less to no effect on altering phagocytic uptake. The data also suggests that these differences are observed even with a dense arrangement of molecules on the surface (dense brush conformation for PEG conjugation), appear to be independent of the serum proteins adsorbing on particles surfaces and is independent of the endocytic uptake pathway. These results provide insight into the differences in the ability of surface modified nano- and micro-particles to avoid phagocytic uptake.”

Thursday, January 17, 2019

PLGA from PolySciTech used in development of nanoparticle-based antisense oligonucleotide delivery system


Antisense oligonucleotides (AS)=O) are synthetic polymers that are short-chain derivatives of DNA or RNA. They can potentially be applied to treating a wide range of diseases by blocking or modifying the synthesis of specific proteins involved in pathological states. However, transporting ASO into the cell where it would work is not easily accomplished. Recently, researchers at University of Copenhagen used PLGA (AP030, AP085, AP054, AP199) from PolySciTech (www.polyscitech.com) as part of designing a nanoparticle system for delivery of antisense oligonucleotides. This research holds promise to enable drug delivery for this class of molecules. Read more: Thanki, Kaushik, Simon Papai, Abhijeet Lokras, Fabrice Rose, Emily Falkenberg, Henrik Franzyk, and Camilla Foged. "Application of a Quality-By-Design Approach to Optimise Lipid-Polymer Hybrid Nanoparticles Loaded with a Splice-Correction Antisense Oligonucleotide: Maximising Loading and Intracellular Delivery." Pharmaceutical Research 36, no. 3 (2019): 37. https://link.springer.com/article/10.1007/s11095-018-2566-3

“Background: Antisense oligonucleotides (ASOs) are promising therapeutics for specific modulation of cellular RNA function. However, ASO efficacy is compromised by inefficient intracellular delivery. Lipid-polymer hybrid nanoparticles (LPNs) are attractive mediators of intracellular ASO delivery due to favorable colloidal stability and sustained release properties. Methods: LPNs composed of cationic lipidoid 5 (L5) and poly(DL-lactic-co-glycolic acid) were studied for delivery of an ASO mediating splice correction of a luciferase gene transcript (Luc-ASO). Specific purposes were: (i) to increase the mechanistic understanding of factors determining the loading of ASO in LPNs, and (ii) to optimise the LPNs and customise them for Luc-ASO delivery in HeLa pLuc/705 cells containing an aberrant luciferase gene by using a quality-by-design approach. Critical formulation variables were linked to critical quality attributes (CQAs) using risk assessment and design of experiments, followed by delineation of an optimal operating space (OOS). Results: A series of CQAs were identified based on the quality target product profile. The L5 content and L5:Luc-ASO ratio (w/w) were determined as critical formulation variables, which were optimised systematically. The optimised Luc-ASO-loaded LPNs, defined from the OOS, displayed high loading and mediated splice correction at well-tolerated, lower doses as compared to those required for reference L5-based lipoplexes, L5-modified stable nucleic acid lipid nanoparticles or LPNs modified with dioleoyltrimethylammonium propane (conventional cationic lipid). Conclusions: The optimal Luc-ASO-loaded LPNs represent a robust formulation that mediates efficient intracellular delivery of Luc-ASO. This opens new avenues for further development of LPNs as a broadly applicable technology platform for delivering nucleic acid cargos intracellularly. Key Words: antisense oligonucleotides in vitro splice correction HeLa pLuc/705 cells lipidoids lipid-polymer hybrid nanoparticles (LPNs) quality-by-design statistical optimization”

Monday, January 14, 2019

PLGA-PEG-PLGA thermogel from PolySciTech used in development of bone-tuberculosis therapy

Although tuberculosis is commonly associated with the lungs, this bacterial infection can also affect other body parts such as the spinal column (Pott’s disease) or long-bones. This form of the disease is both difficult to diagnose (until it is in late stages) and can lead to severe problems, including neurological problems and paralysis. Typically, transfer of medicinal molecules into bone tissue is poor due to weak vascularization and poor blood flow. In this case, achieving a useful concentration of anti-tuberculosis agent in the bones requires very high dosing of the agent throughout the entire body, which can lead to problematic side effects. Recently, researchers at Central South University (China) used PLGA-PEG-PLGA (AK097) from PolySciTech (www.polyscitech.com) to generate Isoniazid loaded hydrogel. Since the gel can be injected directly to site, this could be used to treat bone tuberculosis without requiring a high dose of the drug across the entire body. This research holds promise to improve treatments for this debilitating disease. Read more: Liu, Peng, Binbin Guo, Shengfeng Wang, Jinsong Ding, and Wenhu Zhou. "A Thermo-Responsive and Self-Healing Liposome-in-Hydrogel System as an Antitubercular Drug Carrier for Localized Bone Tuberculosis Therapy." International Journal of Pharmaceutics (2019). https://www.sciencedirect.com/science/article/pii/S0378517319300201

“Abstract: Isoniazid (INH) is a first-line therapy for bone tuberculosis (TB), but its clinic benefits are limited by severe side-effects after long-time administration. While nano-drug delivery systems present as promising strategies for INH delivery, the therapeutic efficacies are usually suboptimal due to ineffective drug accumulation at diseased sites. Local delivery system can achieve high drug concentration at focus sites with minimal systemic exposure, and herein we aimed to employ this strategy to develop a novel liposome-in-hydrogel system for localized treatment of bone TB. To achieve sustainable drug release, a derivative of INH called DINH was loaded because of its hydrophobicity, as well as its better activity and higher biosafety than INH. The hybrid system was demonstrated for thermo-responsive and self-healing properties via phase transition test and rheological studies, which were particularly useful for intra-articular administration. In vivo microdialysis studies revealed that the system can rapidly release drug into synovial fluid to reach effective inhibitory concentrations after localized injection, followed by a steady-state drug release. The optical image studies were performed to study its long-term behavior in vivo, which suggested a sustained drug release profile for several days. This work provides a promising drug delivery system for bone TB therapy. Keywords: Bone tuberculosis Isoniazid Liposomes Thermo-responsive hydrogel Self-healing”

Tuesday, January 8, 2019

PLGA from PolySciTech used in development of oral exenatide formulation for diabetes treatment


Diabetes is a highly prevalent disease affecting roughly 30.3 million Americans, leading to nearly 79,000 deaths annually, making it the 7th leading cause of death (ADA, 2015 statistics). Exenatide is a GLP-1 (glucagon-like peptide-1) agonist used to treat type-2 diabetes. Exenatide’s poor bioavailability requires it to be administered as an injection. Since diabetes is a chronic disease, it is preferable for therapy to be easy for patients to self-administer such as an oral formulation (tablet or pill). Recently, researchers at Yantai University (China) used PLGA (Polyvivo AP081) from PolySciTech (www.polyscitech.com) to develop a nanoparticle-exenatide formulation to improve uptake across the intestine for better bioavailability. This research holds promise for improved treatment options for diabetes. Read more: Song, Yina, Yanan Shi, Liping Zhang, Haiyan Hu, Chunyan Zhang, Miaomiao Yin, Liuxiang Chu et al. "Synthesis of CSK-DEX-PLGA nanoparticles for oral delivery of exenatide to improve its mucus penetration and intestinal absorption." Molecular Pharmaceutics (2019). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.8b00809

“Abstract: Oral absorption of exenatide, a drug for type 2 diabetes treatment, can be improved by using nanoparticles (NPs) for its delivery. To improve the mucus penetration and intestinal absorption of exenatide, we designed a block copolymer, CSKSSDYQC-dextran-poly (lactic-co-glycolic acid) (CSK-DEX-PLGA), and used it for preparation of exenatide-loaded NPs. The functionalized exenatide-loaded NPs composed of CSK-DEX-PLGA were able to target intestinal epithelial cells and reduce the mucus-blocking effect of the intestine. Moreover, the CSK modification of DEX-PLGA was found to significantly promote the absorption efficiency of NPs in the small intestine, based on in vitro ligation of intestinal rings and examination of different intestinal absorption sites. Compared with DEX-PLGA-NPs (DPs), the absorption of CSK-DEX-PLGA-NPs (CDPs) was increased in the villi, allowing the drug to act on goblet-like Caco-2 cells through clathrin-, caveolin- and gap-mediated endocytosis. Furthermore, enhanced transport ability of CDPs was observed in a study on Caco-2/HT-29-MTX co-cultured cells. CDPs exhibited a prolonged hypoglycemic response with a relative bioavailability of 9.2% in diabetic rats after oral administration. In conclusion, CDPs can target small intestinal goblet cells and have a beneficial effect on oral administration of macromolecular peptides as a nanometer-sized carrier.”

Wednesday, January 2, 2019

Just in time for New Years: PLGA-NH2 from PolySciTech used in development of obesity treatment

Around New Year’s, many people begin forming resolutions several of which involve losing weight. There are many causes and factors which contribute to weight gain and obesity. One of which is the disposition of metabolic energy derived from food, whether it is consumed in muscular contractions (exercise), used in biochemical functions (regular homeostasis maintenance), generation of heat or stored as fat. Recently, researchers at Purdue University published a patent describing the use of PLGA-NH2 (Polyyvivo AI010) from PolySciTech (www.polyscitech.com) as part of nanoparticle therapy to encourage fatty cells to convert energy into heat rather than storing it as fat. This research holds promise to help in reduction of obesity and related cardiovascular and other diseases associated with this condition. Read more: Deng, Meng, Chunhui Jiang, Liangju Kuang, and Shihuan Kuang. "Polymer-based therapeutics for inductive browning of fat." U.S. Patent Application 15/771,312, filed November 15, 2018. https://patents.google.com/patent/US20180326080A1/en

“Abstract: This disclosure features the methods and compositions involving development of novel polymer-based therapeutics that induce browning of white adipocytes for the treatment of obesity and its associated metabolic diseases. The therapeutic effects are largely attributed to the promotion of brown and/or beige adipocyte development and function by leveraging adipocyte plasticity and polymer-based drug delivery systems. Both brown and beige adipocytes are densely packed with mitochondria which highly express uncoupling protein-1 (UCP1), a thermogenic protein mediating non-shivering thermogenesis.”

Wednesday, December 12, 2018

Date and Location Set for 2019 BPCR Conference: August 28th KPTC

Last year saw the first annual Biotech, Pharma, Cancer, Research (BPCR) conference sponsored by Akina, Inc. come to beautiful fruition. This scientific networking conference held in Purdue Research Park provides for an opportunity for scientists across academia, corporate, and other institutions to meet and discuss their ideas, needs, and collaboration opportunities. The date and location for 2019 have been set as August 28th in Kurz Purdue Technology Center (KPTC). Keep an eye out for more updates as well as opportunities to present and promote here: http://bpcrconference.com/

Tuesday, December 11, 2018

Amine-PEG-PLGA from PolySciTech used in development of antibiotic formulation against food-borne illness

Although often overlooked, the impact of foodborne illness on society is not trivial. The CDC estimates 48 million are afflicted with 128K hospitalizations and roughly 3000 deaths from foodborne illness each year in USA (https://www.cdc.gov/foodborneburden/index.html). Rosin acids (from conifer trees) are a class of compounds which have good efficacy against a wide range of bacteria, but suffer from poor solubility and side-effects that limits their clinical usefulness. Recently, researchers at the Instituo de Investigacao e Inovacao, em Saude (Portugal) and the Institute of Sciences of Food Production, National Research Council (Italy) used amine-PEG-PLGA (AI058) from PolySciTech (www.polyscitech.com) to create rosin-acid bound nanoparticles and assayed these particles for their efficacy against bacteria. This research holds promise to improve therapies against foodborne illness including antibiotic resistant strains. Read more: Santovito, Elisa, José das Neves, Donato Greco, Vito D’Ascanio, Bruno Sarmento, Antonio Francesco Logrieco, and Giuseppina Avantaggiato. "Antimicrobial properties of rosin acids-loaded nanoparticles against antibiotic-sensitive and antibiotic-resistant foodborne pathogens." Artificial Cells, Nanomedicine, and Biotechnology (2018): 1-9. https://www.tandfonline.com/doi/abs/10.1080/21691401.2018.1496924

“Abstract: Rosin acids (RA) from coniferous trees are used in folk medicine for healing various skin infections. Despite the antimicrobial potential of RA, their poor solubility in aqueous media may limit their use. In this work RA-loaded polyethylene glycol-poly(lactic-co-glycolic acid) nanoparticles (RA-NPs) with enhanced antimicrobial properties against foodborne bacterial pathogens were produced. RA-NPs were prepared by solvent displacement technique and characterized for relevant colloidal features by dynamic light scattering, laser Doppler anemometry and transmission electron microscopy. Association of RA to NPs occurred with high yields (86% w/w). RA and RA-NPs (∼130 nm) were strongly active against antibiotic-sensitive Gram + pathogens, i.e. Clostridium perfringens, Listeria monocytogenes and antibiotic-resistant Staphylococcus aureus. However, both failed in inhibiting the growth of Gram – pathogens (Campylobacter jejuni, Campylobacter coli, Escherichia coli and Salmonella enterica). Association to NPs enhanced the antimicrobial activity of RA. MIC, IC50, IC90, and MBC values of RA-NPs were ten-times lower than RA. RA-NPs did not change the intrinsic toxicity potential of RA. This is the first study on the enhancement of the antimicrobial activity of RA when associated to nanocarriers. This approach may be an effective strategy to produce aqueous-based RA solutions with enhanced antimicrobial activity against antibiotic-sensitive and antibiotic-resistant Gram + pathogens. Keywords: Nanoparticles, antimicrobials, rosinic acids, pathogenic bacteria, nanocarriers”

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