Journal
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume 54, Issue 13, Pages 7983-7989Publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.13-13068
Keywords
choroidal neovascularization; targeted PDT; anti-VEGF; photocyanine; sorafenib; RGD peptide; liposomes
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Funding
- National Science Foundation [81130059]
- Ministry of Science and Technology of China [2009CB930300, 2009ZX09310-001]
- Ministry of Education [BMU20110263]
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PURPOSE. To achieve a combination therapy of targeted PDT and anti-VEGF for choroidal neovascularization (CNV). METHODS. Arg-Gly-Asp (RGD)-modified liposomes encapsulating photocyanine and sorafenib (RGD-SSL-[P]-[S]) were prepared and characterized. Drug concentration in RGD-SSL-[P]-[S] and irradiation time were optimized on ARPE-19 and HUVEC cells in vitro. A laser-induced CNV rat model was used to assess the efficacy of this targeted combinational system. The effect of RGD-SSL-[P]-[S] on the retinal structure of BN rats was also examined. RESULTS. The particle size of RGD-SSL-[P]-[S] was approximately 100 nm, with a encapsulation efficiency more than 90% for both photocyanine and sorafenib. From RGD-SSL-[P]-[S], the release rate of photocyanine was approximately 22%, whereas that of sorafeinb was approximately 40% at 48 hours. With the optimal drug concentration and irradiation time, RGD-SSL-[P]-[S] exhibited cytotoxicity only to HUVEC without obvious damage to normal ARPE-19 cells. Rats treated with RGD-SSL-[P]-[S] showed the least CNV area and fluorescein leakage in fluorescein fundus angiography. RGD-SSL-[P]-[S] was also found safe to the rat retina. CONCLUSIONS. Combination of targeted PDT and anti-VEGF might be an effective therapy for CNV.
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