Tuesday, June 30, 2015

Fluorescent PolyVivo PLGA-FPR648 used for tracking nanoparticles as part of oral insulin delivery

PolySciTech (www.polyscitech.com) provides a wide array of biodegradable polymers including fluorescently tagged PLGA. Recently, PolyVivo AV008 (PLGA-FPR648 conjugate) was used as part of research in the development of PLGA nanoparticles for oral insulin delivery. The particles were coated with a chitosan based shell to impart mucoadhesion to the particles for insulin delivery. Use of AV008 made the particles visible under microscopy so that their uptake in Caco-2 cells could be tracked more easily to determine nanoparticle fate. Read more: Sheng, Jianyong, Limei Han, Jing Qin, Ge Ru, Ruixiang Li, Lihong Wu, Dongqi Cui, Pei Yang, Yuwei He, and Jianxin Wang. "N-trimethyl Chitosan Chloride-Coated PLGA Nanoparticles Overcoming Multiple Barriers to Oral Insulin Absorption." ACS Applied Materials & Interfaces (2015). http://pubs.acs.org/doi/abs/10.1021/acsami.5b03555

“Abstract: Although several strategies have been applied for oral insulin delivery to improve insulin bioavailability, little success has been achieved. To overcome multiple barriers to oral insulin absorption simultaneously, insulin-loaded N-trimethyl chitosan chloride (TMC)-coated polylactide-co-glycoside (PLGA) nanoparticles (Ins TMC-PLGA NPs) were formulated in our study. The Ins TMC-PLGA NPs were prepared using the double-emulsion solvent evaporation method and were characterized to determine their size (247.6±7.2 nm), zeta potential (45.2±4.6 mV), insulin-loading capacity (7.8±0.5%) and encapsulation efficiency (47.0±2.9%). The stability and insulin release of the nanoparticles in enzyme-containing simulated gastrointestinal fluids suggested that the TMC-PLGA NPs could partially protect insulin from enzymatic degradation. Compared with unmodified PLGA NPs, the positively charged TMC-PLGA NPs could improve the mucus penetration of insulin in mucus-secreting HT29-MTX cells, the cellular uptake of insulin via clathrin- or adsorption-mediated endocytosis in Caco-2 cells, and the permeation of insulin across a Caco-2 cell monolayer through tight junction opening. After oral administration in mice, the TMC-PLGA NPs moved more slowly through the gastrointestinal tract compared with unmodified PLGA NPs, indicating the mucoadhesive property of the nanoparticles after TMC coating. Additionally, in pharmacological studies in diabetic rats, orally administered Ins TMC-PLGA NPs produced a stronger hypoglycemic effect, with 2-fold higher relative pharmacological availability compared with unmodified NPs. In conclusion, oral insulin absorption is improved by TMC-PLGA NPs with the multiple absorption barriers overcome simultaneously. TMC-PLGA NPs may be a promising drug delivery system for oral administration of macromolecular therapeutics.”
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