School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
Int J Pharm. 2010 Dec 15;402(1-2):248-53. doi: 10.1016/j.ijpharm.2010.10.008. Epub 2010 Oct 8.
Ophthalmic drug delivery with long pre-corneal retention time and high penetration into aqueous humor and intraocular tissues is the key-limiting factor for the treatment of ocular diseases and disorders. Within this study, the conjugate of cysteine-polyethylene glycol monostearate (Cys-PEG-SA) was synthesized and was used to compose the thiolated nanostructured lipid carrier (Cys-NLC) as a potential nanocarrier for the topical ocular administration of cyclosporine A (CyA). The rapid cross-linking process of Cys-PEG-SA in vitro was found in simulated physiological environment. The in vitro CyA release from Cys-NLC was slower than that of non-thiolated nanostructured lipid carriers (NLC) due to the cross-linking of thiomers on the surface of nanocarriers. After topical ocular administration in rabbits, the in vivo ocular distribution of CyA was investigated in comparison of Cys-NLC with non-thiolated NLCs and oil solution. The results showed that CyA concentration in systemic blood was very low and close to the detection limit. The area-under-the-curve (AUC(0-24h)) and mean retention time (MRT(0-24h)) of Cys-NLC group in aqueous humor, tear and eye tissues were significantly higher than that of oil solution, non-thiolated NLCs (p<0.05). These results demonstrated that the thiolated NLC could deliver high level of CyA into intraocular tissues due to its bioadhesive property and sustained release characteristics.
具有较长的角膜前滞留时间和高穿透性进入房水和眼内组织的眼科药物传递是治疗眼部疾病和障碍的关键限制因素。在本研究中，合成了半胱氨酸-聚乙二醇单硬脂酸酯（Cys-PEG-SA）的缀合物，并将其用于组成巯基化的纳米结构脂质载体（Cys-NLC），作为环孢素 A（CyA）局部眼用的潜在纳米载体。在模拟生理环境中发现了 Cys-PEG-SA 的快速交联过程。由于纳米载体表面上的硫醇的交联，Cys-NLC 中 CyA 的体外释放比非巯基化的纳米结构脂质载体（NLC）缓慢。在兔体内局部眼部给药后，将 Cys-NLC 与非巯基化的 NLC 和油溶液进行比较，研究了 CyA 的体内眼分布。结果表明，CyA 在全身血液中的浓度非常低，接近检测限。与油溶液相比，Cys-NLC 组在房水、泪液和眼组织中的 AUC(0-24h)和 MRT(0-24h)明显更高（p<0.05）。这些结果表明，由于其生物黏附特性和持续释放特性，巯基化的 NLC 可以将高水平的 CyA 递送到眼内组织中。
