Tumor delivery of liposomal doxorubicin prepared with poly-L-glutamic acid as a drug-trapping agent.
J Liposome Res
; 27(2): 99-107, 2017 Jun.
Article
en En
| MEDLINE
| ID: mdl-26982164
CONTEXT: Poly-l-glutamic acid (PGA) is an anionic polymer with a large number of carboxyl groups that can interact electrostatically with cationic drugs such as doxorubicin (DOX). OBJECTIVE: For stable encapsulation of DOX into liposomes, we prepared triethylamine (TEA)-PGA-liposomes using PGA as an internal trapping agent. METHODS: We prepared TEA-PGA-liposomes by remote loading of DOX with a TEA gradient into preformed liposomes prepared with 1, 2, or 4 mg/mL PGA (molecular weights 4800, 9800, and 20 500), and evaluated their biodistribution and antitumor effects on Lewis lung carcinoma (LLC) tumor-bearing mice. RESULTS: TEA-PGA-liposomes using the higher the molecular weight or concentration of PGA showed a slower release of DOX from the liposomes. TEA-PGA-liposomes prepared with a high concentration of PGA could enhance DOX accumulation in tumors and prolonged DOX circulation in the serum, indicating that DOX may be retained stably in the liposomal interior by interaction with PGA. Furthermore, injection of TEA-PGA-liposomes prepared with 4 mg/mL of PGA9800 or 2 mg/mL PGA20500 strongly inhibited tumor growth in LLC tumor-bearing mice. CONCLUSIONS: PGA may be a potential trapping agent for liposomal DOX for tumor drug delivery.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ácido Poliglutámico
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Doxorrubicina
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Sistemas de Liberación de Medicamentos
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Carcinoma Pulmonar de Lewis
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Antineoplásicos
Límite:
Animals
Idioma:
En
Revista:
J Liposome Res
Asunto de la revista:
BIOQUIMICA
Año:
2017
Tipo del documento:
Article
Pais de publicación:
Reino Unido