title: Preparation and pharmacodynamics of stearic acid and poly (lactic-co-glycolic acid) grafted chitosan oligosaccharide micelles for 10-hydroxycamptothecin.
abstract: Stearic acid (SA) and poly (lactic-co-glycolic acid) (PLGA) grafted chitosan oligosaccharide (SA-CSO-PLGA SCP) tripolymer was synthesized via the reaction between the carboxyl group of SA or PLGA with carboxylic side group, and the amine group of CSO in the presence of 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). The degrees of amino-substitution for SA and PLGA were assayed through 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) test and (13)C NMR spectrum, which were 8.15% and 5.82%, respectively; the critical micelle concentrations of SCP in PBS (pH 7.4) and deionized water (DI water) were about 34.9 and 14.5 microg/ml, respectively. Using 10-hydroxycamptothecin (HCPT) as a model drug, the drug-loaded micelles showed above 86% encapsulation efficiency, which not only enhanced the solubility of HCPT in aqueous medium markedly, but also protected the lactone ring of HCPT. Cellular uptakes of SCP micelles against A549, MCF-7 and HepG-2 tumor cells showed a faster cellular internalization. Comparing to the commercial HCPT injection, HCPT-loaded micelles showed higher cytotoxicities against A549, MCF-7 and HepG-2 cells. The increased folds were 22, 18 and 15, respectively. These results suggested the SCP could be applied as a carrier for hydrophobic drugs.
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang Road, Nanjing 210009, PR China.
authors.forename: Yue-Yu
authors.initials: YY
authors.lastname: Zhou
authors.forename: Yong-Zhong
authors.initials: YZ
authors.lastname: Du
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zhou
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Hu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002234:Carbodiimides / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D056945:Hep G2 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D019344:Lactic Acid / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D010316:Particle Size; D011100:Polyglycolic Acid / Q000138:chemical synthesis*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility; D013229:Stearic Acids / Q000138:chemical synthesis*; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: C518491:1-ethyl-3-(3-(diethylamino)propyl)carbodiimide; D000972:Antineoplastic Agents, Phytogenic; D002234:Carbodiimides; D004337:Drug Carriers; D008823:Micelles; D013229:Stearic Acids; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C031183:stearic acid; D048271:Chitosan; C028098:10-hydroxycamptothecin; D002166:Camptothecin