Preparation and anti-tumor effect in vitro of doxorubicin-loaded targeting micelles modified by folic acid / 中国药学杂志
Chinese Pharmaceutical Journal
;
(24): 990-995, 2013.
Artigo
em Chinês
| WPRIM
| ID: wpr-860349
ABSTRACT
OBJECTIVE:
To prepare doxorubicin (DOX)-loaded micelles based on folic acid-modified cholesterol-glycol chitosan (FCHGC), and study its physicochemical properties and cytotoxicity in vitro.METHODS:
FCHGC copolymer was synthesized by conjugating carboxyl groups of folic acid with the primary amino groups of cholesterol-modified glycol chitosan (CHGC) in the presence of coupling agent. FCHGC conjugate was characterized by 1H-NMR and fluorescence measurement using pyrene as a probe. The DOX-loaded micelles were prepared by an emulsion/solvent evaporation method. The size and shape of the micelles were analyzed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). DOX release behavior was studied in vitro by a dialysis method in phosphate buffer saline (PBS, pH 7.4). The cytotoxicity and celluar uptake of drug-loaded micelles in vitro were investigated by 3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry.RESULTS:
The critical aggregation concentration (CAC) of the FCHGC micelles in aqueous solution was 0.0163 mg·mL-1. Its particle size was 227 nm. The drug loading and encapsulation efficiency of DOX-loaded FCHGC (DFCHGC) micelles were 10.5% and 78.5%, respectively. The shape of DFCHGC micelles was almost spherical. DOX was released from DOX-loaded micelles in a biphasic manner, which displayed an initial rapid release phase and a later sustained release phase. The 50% inhibitory concentrations (IC50) of DOX, DOX-loaded CHGC (DCHGC) and DFCHGC micelles, incubated with folate receptor (FR)-negative A549 cells for 48 h, were 1.493, 0.620 and 0.974 μg·mL-1, respectively. Therefore, DCHGC micelles exhibited much more potent cytotoxicity against A549 cells than DFCHGC micelles. In FR-positive HeLa cells, the IC50 values of DOX, DCHGC and DFCHGC micelles were 1.398, 0.662 and 0.259 μg·mL-1, respectively. The DFCHGC micelles showed the greatest cytotoxicity among three DOX formulations for HeLa cells. And DFCHGC micelles exhibited greater cellular uptake than free DOX and DCHGC micelles in HeLa cells.CONCLUSION:
The FCHGC micelles as a drug carrier for DOX delivery show selectively targeting to FR-positive cells, and improve the anti-tumor activity of DOX. These results suggested that FCHGC micelles could be a potential carrier for active targeting drug delivery.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Idioma:
Chinês
Revista:
Chinese Pharmaceutical Journal
Ano de publicação:
2013
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS