title: Chitosan surface-modified hydroxycamptothecin loaded nanoparticles with enhanced transport across Caco-2 cell monolayer.
abstract: This study explored the feasibility of using surface-modified nanoparticulate drug delivery system to enhance the transepithelial transport of antitumor drugs. An antitumor drug, 10-hydroxycamptothecin, was encapsulated into nanoparticles made of biodegradable poly(caprolactone-co-lactide)-PEG-poly(caprolactone-co-lactide) by a novel two-step nano-precipitation method. The obtained nanoparticles had a drug loading content of 10.4% and a size of 256.3 nm, exhibiting a steady and sustained in vitro release profile. By incubation in chitosan containing medium, the drug-loaded nanoparticles could be subsequently surface-modified with chitosan. The surface modification was monitored by dynamic light scattering method, zeta potential observation, and transmission electron microscopy, and its degree could be easily adjusted by varying the concentration of chitosan in the incubation medium. Caco-2 cell monolayer was used as an in vitro model to evaluate the intestinal 10-hydroxycamptothecin absorption. The absorptive transport of 10-hydroxycamptothecin could be improved to some extent by drug loaded nanoparticles and could be further enhanced in the case of surface-modified nanoparticles, suggesting that chitosan surface-modified nanoparticles may be a promising oral delivery system for antitumor drugs.
authors.affiliation: Laboratory of Mesoscopic Chemistry, Department of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
authors.forename: Leyang
authors.initials: L
authors.lastname: Zhang
authors.forename: Minjie
authors.initials: M
authors.lastname: Sun
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Jiang
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiqun
authors.initials: X
authors.lastname: Jiang
authors.forename: Changzheng
authors.initials: C
authors.lastname: Yang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001693:Biological Transport, Active; D018938:Caco-2 Cells; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D048271:Chitosan / Q000737:chemistry*; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D003460:Crystallization / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D008422:Materials Testing; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D013499:Surface Properties
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D048271:Chitosan; C028098:10-hydroxycamptothecin; D002166:Camptothecin