title: Incorporation of camptothecin into N-phthaloyl chitosan-g-mPEG self-assembly micellar system.
abstract: The capability of N-phthaloylchitosan-grafted poly (ethylene glycol) methyl ether (mPEG)(PLC-g-mPEG) to enhance the aqueous solubility and stability of the lactone form of camptothecin (CPT) was investigated. PLC-g-mPEG formed a core-shell micellar structure after dialysis of the polymer solutions in dimethyl sulfoxide (DMSO) or dimethylformamide (DMF) against water, with a critical micelle concentration (CMC) of 28 microg/ml. CPT was loaded into the inner core of the micelles by dialysis method. The results showed an increase in the CPT-loading amount with an increasing concentration of CPT. The stability of drug-loaded micelles was studied by gel-permeation chromatography (GPC), and their in vitro release behaviors were analyzed. Release of CPT from the micelles was sustained. When compared to the unprotected CPT, CPT-loaded PLC-g-mPEG micelles were able to prevent the hydrolysis of the lactone group of the drug. The kinetics of the CPT hydrolysis in human serum albumin (HSA) and fetal bovine serum (FBS) were pseudo-first order. The hydrolysis rate constants for CPT and CPT-loaded PLC-g-mPEG micelles in phosphate-buffered saline (PBS) pH 7.4, were 7.4 x 10(-3) min(-1) and 9.1 x 10(-3) h(-1), parallel to an increase in half-life of CPT from 94 min to 76.15 h, respectively.
authors.affiliation: Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand. Praneet@email.pharm.su.ac.th
authors.forename: Praneet
authors.initials: P
authors.lastname: Opanasopit
authors.forename: Tanasait
authors.initials: T
authors.lastname: Ngawhirunpat
authors.forename: Amornrut
authors.initials: A
authors.lastname: Chaidedgumjorn
authors.forename: Theerasak
authors.initials: T
authors.lastname: Rojanarata
authors.forename: Auayporn
authors.initials: A
authors.lastname: Apirakaramwong
authors.forename: Sasiprapha
authors.initials: S
authors.lastname: Phongying
authors.forename: Chantiga
authors.initials: C
authors.lastname: Choochottiros
authors.forename: Suwabun
authors.initials: S
authors.lastname: Chirachanchai
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry*; D002166:Camptothecin / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D006868:Hydrolysis; D007700:Kinetics; D007783:Lactones / Q000737:chemistry; D008823:Micelles; D008956:Models, Chemical; D011092:Polyethylene Glycols / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012995:Solubility; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007783:Lactones; D008823:Micelles; C515873:N-phthaloyl chitosan-graft-poly(ethylene glycol) methyl ether; D012709:Serum Albumin; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D048271:Chitosan; D002166:Camptothecin