tailieunhanh - báo cáo khoa học: "Development of PEGylated PLGA nanoparticle for controlled and sustained drug delivery in cystic fibrosis"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Development of PEGylated PLGA nanoparticle for controlled and sustained drug delivery in cystic fibrosis | Vij et al. Journal of Nanobiotechnology 2010 8 22 http content 8 1 22 JOURNAL OF NANOBIOTECHNOLOGY RESEARCH Open Access Development of PEGylated PLGA nanoparticle for controlled and sustained drug delivery in cystic fibrosis 1 1 1133 Neeraj Vij Taehong Min Rhul Marasigan Christopher N Belcher Steven Mazur Hong Ding Ken-Tye Yong Indrajit Roy3 Abstract Background The mutation in the cystic fibrosis transmembrane conductance regulator CFTR gene results in CF. The most common mutation AF508-CFTR is a temperature-sensitive trafficking mutant with reduced chloride transport and exaggerated immune response. The AF508-CFTR is misfolded ubiquitinated and prematurely degraded by proteasome mediated- degradation. We recently demonstrated that selective inhibition of proteasomal pathway by the FDA approved drug PS-341 pyrazylcarbonyl-Phe-Leuboronate . Velcade or bortezomib ameliorates the inflammatory pathophysiology of CF cells. This proteasomal drug is an extremely potent stable reversible and selective inhibitor of chymotryptic threonine protease-activity. The apprehension in considering the proteasome as a therapeutic target is that proteasome inhibitors may affect proteostasis and consecutive processes. The affect on multiple processes can be mitigated by nanoparticle mediated PS-341 lungdelivery resulting in favorable outcome observed in this study. Results To overcome this challenge we developed a nano-based approach that uses drug loaded biodegradable nanoparticle PLGA-PEGps-341 to provide controlled and sustained drug delivery. The in vitro release kinetics of drug from nanoparticle was quantified by proteasomal activity assay from days 1-7 that showed slow drug release from day 2-7 with maximum inhibition at day 7. For in vivo release kinetics and biodistribution these drug-loaded nanoparticles were fluorescently labeled and administered to C57BL6 mice by intranasal route. Whole-body optical imaging of the treated live animals .