Drug Delivery with Hyaluronic Acid-Coated Polymeric Micelles in Liver Fibrosis Therapy.
ACS Biomater Sci Eng
; 9(6): 3414-3424, 2023 06 12.
Article
em En
| MEDLINE
| ID: mdl-37159164
ABSTRACT
Developing delivery vehicles that achieve drug accumulation in the liver and transferability into hepatic stellate cells (HSCs) across the liver sinusoidal endothelium is essential to establish a treatment for hepatic fibrosis. We previously developed hyaluronic acid (HA)-coated polymeric micelles that exhibited affinity to liver sinusoidal endothelial cells. HA-coated micelles possess a core-shell structure of self-assembled biodegradable poly(l-lysine)-b-poly(lactic acid) AB-diblock copolymer (PLys+-b-PLLA), and its exterior is coated with HA through polyion complex formation via electrostatic interaction between anionic HAs and cationic PLys segments. In this study, we prepared HA-coated micelles entrapping olmesartan medoxomil (OLM), an anti-fibrotic drug, and evaluated their possibility as drug delivery vehicles. HA-coated micelles exhibited specific cellular uptake into LX-2 cells (human HSC line) in vitro. In vivo imaging analysis after intravenous (i.v.) injection of HA-coated micelles into mice revealed that the micelles exhibited high accumulation in the liver. Observation of mouse liver tissue sections suggested that HA-coated micelles were distributed in liver tissue. Furthermore, i.v. injection of HA-coated micelles entrapping OLM showed a remarkable anti-fibrotic effect against the liver cirrhosis mouse model. Therefore, HA-coated micelles are promising candidates as drug delivery vehicles for the clinical management of liver fibrosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Hialurônico
/
Micelas
Limite:
Animals
/
Humans
Idioma:
En
Revista:
ACS Biomater Sci Eng
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Japão