title: Development and in vitro evaluation of surface modified poly(lactide-co-glycolide) nanoparticles with chitosan-4-thiobutylamidine.
abstract: The objective of this study was to develop a nanoparticulate drug delivery system based on the surface modification of poly(lactide-co-glycolide) (PLGA) nanoparticles with a thiolated chitosan. PLGA nanoparticles were prepared by the emulsification-solvent evaporation method. Immobilization of chitosan to the surface of PLGA nanoparticles via amide bonds was mediated by a carbodiimide. Thiol groups were covalently bound to the chitosan surface of particles by reaction with 2-iminothiolane. Obtained nanoparticles were characterized in vitro regarding size, zeta potential, thiol group content, stability at different pH values, mucoadhesion, and drug release. Results demonstrated that the surface modification of PLGA nanoparticles with thiolated chitosan (chitosan-TBA) leads to nanoparticles of a mean diameter of 889.5 +/- 72 nm and positive zeta potential of + 24.74 mV. The modified nanoparticles contained 7.32 +/- 0.24 micromol thiol groups per gram nanoparticles. The size of nanoparticles was strongly influenced by the pH of the surrounding medium, being 925.0 +/- 76.3 nm at pH 2 and 577.8 +/- 66.7 nm at pH 7.4. Thiolated nanoparticles showed a 3.3-fold prolonged residence time on the mucosa and an unchanged release profile in comparison to unmodified PLGA nanoparticles. These data suggest that surface modified chitosan-TBA conjugate PLGA nanoparticles have the potential to be used as mucoadhesive drug delivery system.
authors.affiliation: Institute of Pharmacy, Department of Pharmaceutical Technology, University of Innsbruck, Austria.
authors.forename: Vjera
authors.initials: V
authors.lastname: Grabovac
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000268:Adhesiveness; D000818:Animals; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry; D003474:Curcumin / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa; D007421:Intestine, Small; D019344:Lactic Acid / Q000737:chemistry*; D009092:Mucous Membrane; D053758:Nanoparticles / Q000737:chemistry*; D010084:Oxidation-Reduction; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D013499:Surface Properties; D013552:Swine
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011108:Polymers; C493042:chitosan-4-thiobutylamidine; D002686:Chitin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003474:Curcumin