EphA2 targeted doxorubicin stealth liposomes as a therapy system for choroidal neovascularization in rats.
Invest Ophthalmol Vis Sci
; 53(11): 7348-57, 2012 Oct 23.
Article
em En
| MEDLINE
| ID: mdl-22977140
ABSTRACT
PURPOSE:
To enhance drug uptake in RPE cells, improve efficacy for choroidal neovascularization (CNV), and reduce drug toxicity, an EphA2-targeted nanocarrier loaded with doxorubicin (DOX) was developed by conjugation with a homing peptide YSA.METHODS:
The YSA was coupled to PEGylated lipid. Then, YSA-modified DOX stealth liposomes (YSA-SSL-DOX) were prepared and characterized. Their uptake in a human RPE cell line (ARPE-19) was evaluated. After intravitreous injection, their efficacy against CNV was assessed in a laser-induced rat model. Finally, TUNEL test and morphology observation on rat retina were conducted.RESULTS:
The prepared YSA-SSL-DOX was approximately 110 nm in particle size, with an encapsulation efficiency of DOX more than 95%. The leakage of DOX from YSA-SSL-DOX was very slow. The expression of EphA2 on the CNV was confirmed. Both flow cytometry and confocal microscopy studies revealed that YSA-SSL-DOX could facilitate the uptake of liposomal DOX into ARPE-19 cells. Treatment with YSA-SSL-DOX (2.5 µg DOX) resulted in a significant reduction in the CNV area of rats compared with the unmodified liposomal DOX and normal saline (P < 0.05). No obvious toxicity of YSA-SSL-DOX on rat retina was found.CONCLUSIONS:
EphA2-targeted stealth liposomes might be an effective delivery and therapy system for angiogenesis-related diseases in the retina.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polietilenoglicóis
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Doxorrubicina
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Neovascularização de Coroide
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Receptor EphA2
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
Ano de publicação:
2012
Tipo de documento:
Article