Targeted delivery of platinum-taxane combination therapy in ovarian cancer.
J Control Release
; 220(Pt B): 651-9, 2015 Dec 28.
Article
en En
| MEDLINE
| ID: mdl-26381902
ABSTRACT
Biodegradable polypeptide-based nanogels have been developed from amphiphilic block copolymers, poly(ethylene glycol)-b-poly(L-glutamic acid)-b-poly(L-phenylalanine), which effectively co-incorporate cisplatin and paclitaxel, the clinically used drug combination for the treatment of advanced ovarian cancer. In order to target both drugs selectively to the tumor cells, we explored the benefits of ligand-mediated drug delivery by targeting folate receptors, which are overexpressed in most ovarian cancers. Drug-loaded nanogels were surface-functionalized with folic acid (FA) with the help of a PEG spacer without affecting the ligand binding affinity and maintaining the stability of the carrier system. FA-decorated nanogels significantly suppressed the growth of intraperitoneal ovarian tumor xenografts outperforming their nontargeted counterparts without extending their cytotoxicity to the normal tissues. We also confirmed that synchronized co-delivery of the platinum-taxane drug combination via single carrier to the same targeted cells is more advantageous than a combination of targeted single drug formulations administered at the same drug ratio. Lastly, we demonstrated that the same platform can also be used for localized chemotherapy. Our data indicate that intraperitoneal administration can be more effective in the context of targeted combination therapy. Our findings suggest that multifunctional nanogels are promising drug delivery carriers for improvement of current treatment for ovarian cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Neoplasias Ováricas
/
Polímeros
/
Portadores de Fármacos
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Cisplatino
/
Paclitaxel
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
J Control Release
Asunto de la revista:
FARMACOLOGIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos