Journal
DRUG DELIVERY
Volume 26, Issue 1, Pages 989-1001Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10717544.2019.1667455
Keywords
PAMAM dendrimer; cyclic RGD hexapeptide; penetratin; nanocarriers; ocular posterior segment
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Funding
- Natural Science Foundation of Shandong [ZR2014HM062]
- National Science and Technology Major Project [2018ZX09301-017-003]
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Noninvasive drug delivery is a promising treatment strategy for ocular posterior segment diseases. Many physiological and anatomical barriers of the eye considerably restrict effective diffusion of therapeutics to the target site. To overcome this problem, a novel cyclic arginine-glycine-aspartate (RGD) hexapeptide and penetratin (PEN) co-modified PEGylation polyamidoamine (PAMAM) was designed as a nanocarriers (NCs), and its penetrating and targeting abilities were evaluated. In this study, we show that PAMAM-PEG (reaction molar ratio 1:32) has a relatively high grafting efficiency and low cytotoxicity. The particle size was within the range of 15?20?nm after modification with RGD and PEN. Cellular uptake of RGD-modified NCs involved significant affinity toward integrin ?v?3, which validated the targeting of neovasculature. An in vitro permeation study indicated that modification with PEN significantly improved penetration of the NCs (1.5 times higher). In vivo ocular distribution studies showed that, the NCs (modified with PEN or co-modified with RGD and PEN) were highly distributed in the cornea and retina (p?
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