期刊
MOLECULAR PHARMACEUTICS
卷 11, 期 4, 页码 1218-1227出版社
AMER CHEMICAL SOC
DOI: 10.1021/mp400681n
关键词
cell-penetrating peptide; penetratin; ocular drug delivery; permeability; toxicity
资金
- National Natural Science Fund of China [81172994]
- National Science and Technology Major Project [2012ZX09304004]
- Shanghai Science and Technology Committee [11431921200]
Intraocular drug delivery is extraordinarily hampered by the impermeability of defensive barriers of the eye. In this study, the ocular permeability of fluorophore-labeled cell-penetrating peptides (CPPs), including penetratin, TAT, low molecular weight protamine, and poly(arginine)(8), was investigated based on multilevel evaluations. The human conjunctival epithelial cell (NHC) was exposed to various CPPs to determine the cytotoxicity and cellular uptake. Ex vivo studies with rabbit cornea were performed using side-by-side diffusion chambers to evaluate the apparent permeability coefficients and acute tissue tolerance of the CPP candidates. Among all examined CPPs, penetratin shows an outstanding cellular uptake, by increasing more than 16 and 25 times at low and high concentrations, compared to the control peptide poly(serine)(8) respectively. Additionally, the permeability of penetratin across excised cornea is 87.5 times higher in comparison with poly(serine)(8). More importantly, after instilled in the conjunctival sac of rat eyes, fluorophore-labeled penetratin displayed a rapid and wide distribution in both anterior and posterior segment of the eye, and could be observed in the corneal epithelium and retina lasting for at least 6 h. Interestingly, penetratin showed the lowest ocular cell and tissue toxicities among all examined CPPs. The high ocular permeability of penetratin could be attributed to its amphipathicity and spatial conformation determined by circular dichroism. Taken together, these data demonstrate that penetratin is potentially useful as an absorption enhancer for intraocular drug delivery.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据