title: Glucosylated polymeric nanoparticles: a sweetened approach against blood compatibility paradox.
abstract: Surface functionalization strategies in generating stealth nano-carriers have garnered considerable attention in pharmaceutical research. In this regard, our investigation reports on the preparation and evaluation of glucose decorated poly lactic-co-glycolic acid (PLGA) nanoparticles as blood compatible nanoparticulate drug delivery system, with enhanced cellular uptake. Terminal carboxylic acid groups on PLGA were modified with the amino group of glucosamine and nanoparticles were generated by modified solvent diffusion (nano-precipitation) technique. Detailed in vitro experiments were performed to evaluate the eminence of glucose functionalization over unmodified nanoparticles, in terms of their hemocompatibility and cellular uptake. Glucosylation was confirmed by NMR and FTIR spectroscopy; PLGA and modified particles had average size in the range of 125nm. Glucosylation was an effective strategy in reducing plasma protein adsorption, complement activation and platelet plugging of PLGA nanoparticles. PLGA and their glucose modified versions were quite compatible with the blood cells and were non-cytotoxic. Moreover the uptake behaviour of glucose modified PLGA nanoparticles were enhanced in comparison to standard PLGA nanoparticles as emphasized by the z stacking analysis following confocal imaging. Precisely the stealth properties of glucose modified PLGA nanoparticles (PLGA-Glu), with enhanced cellular internalization, seems to be a safe and efficient system for intravenous drug delivery applications.
authors.affiliation: Division of Biosurface Technology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram 695012, Kerala, India.
authors.forename: Y M
authors.initials: YM
authors.lastname: Thasneem
authors.forename: S
authors.initials: S
authors.lastname: Sajeesh
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Sharma
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000494:pharmacology; D001692:Biological Transport; D001798:Blood Proteins / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods; D005944:Glucosamine / Q000737:chemistry*; D005947:Glucose / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D001798:Blood Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005947:Glucose; D005944:Glucosamine