RESUMO
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.
Assuntos
Antineoplásicos Fitogênicos/química , Camptotecina/química , Quitosana/análogos & derivados , Portadores de Fármacos , Micelas , Polietilenoglicóis/química , Química Farmacêutica , Quitosana/química , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Preparações de Ação Retardada , Composição de Medicamentos , Estabilidade de Medicamentos , Hidrólise , Cinética , Lactonas/química , Modelos Químicos , Albumina Sérica/química , Soroalbumina Bovina/química , Solubilidade , Fatores de TempoRESUMO
A novel type of chitosan nanoscaffold with a soft and cotton-like appearance is proposed. The key to success is based on two points: (i) the change in morphology of chitin whisker to chitosan nanoscaffold and (ii) the surface modification of the nanoscaffold chitosan with a sugar unit. Simple deacetylation of chitin whisker gives a colloidal solution of chitosan, of which the chitosan is in a nanoscaled scaffold. Surface functionalization of the chitosan nanoscaffold with lactose or maltose via a heterogeneous system in water at room temperature results in a soft and cotton-like chitosan containing mesopores. As all steps are organic solvent free, this chitosan-sugar nanoscaffold might be a promising material for biopolymer-supported tissue engineering.
