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
em En
| MEDLINE
| ID: mdl-26982164
ABSTRACT
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Poliglutâmico
/
Doxorrubicina
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Sistemas de Liberação de Medicamentos
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Carcinoma Pulmonar de Lewis
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Antineoplásicos
Limite:
Animals
Idioma:
En
Revista:
J Liposome Res
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2017
Tipo de documento:
Article