The bifunctional liposomes constructed by poly(2-ethyl-oxazoline)-cholesteryl methyl carbonate: an effectual approach to enhance liposomal circulation time, pH-sensitivity and endosomal escape.
Pharm Res
; 31(11): 3038-50, 2014 Nov.
Article
en En
| MEDLINE
| ID: mdl-24805279
ABSTRACT
PURPOSE:
A novel bifunctional liposome with long-circulating and pH-sensitive properties was constructed using poly(2-ethyl-oxazoline)-cholesteryl methyl carbonate (PEtOz-CHMC) in this study.METHODS:
PEtOz-CHMC was synthesized and characterized by TLC, IR and (1)H-NMR. The obtained PEtOz lipid was inserted into liposomes by the post-insertion method. Through a series of experiments, such as drug release, tumor cell uptake, cytotoxicity, calcium-induced aggregation, pharmacokinetic experiments, etc., the pH-sensitive and long-circulating properties of PEtOzylated liposomes was identified.RESULTS:
PEtOz-CHMC modified liposomes (PEtOz-L) showed increased calcein release at low pH. Flow cytometric analysis results showed that the fusion and cellular uptake of PEtOz-L could be promoted significantly at pH 6.4 compared with those at pH 7.4. Confocal laser scanning microscope observations revealed that PEtOz-L could respond to low endosomal pH and directly released the fluorescent tracer into the cytoplasm. MTT assays in HeLa cells demonstrated that doxorubicin hydrochloride (DOX) loaded PEtOz-L exhibited stronger anti-tumor activity in a medium at pH 6.4 than in a medium pH 7.4. PEtOz-L remained stable when these liposomes were incubated in calcium chloride solution. The cumulative calcein release rate of PEtOz-L was significantly lower than that of CL when the liposomes were dialysed in PBS. The pharmacokinetic experiments of liposomes in rats showed that t 1/2 and AUC of PEtOz-L were 4.13 times and 4.71 times higher than those of CL.CONCLUSIONS:
PEtOzylated liposomes exhibits excellent long-circulating and pH-sensitive properties. Our results suggest that PEtOz is a promising biomaterial for the modification of liposome in drug delivery.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Poliaminas
/
Endosomas
/
Tiempo de Circulación Sanguínea
/
Formiatos
/
Liposomas
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Pharm Res
Año:
2014
Tipo del documento:
Article