Improved ocular bioavailability of indomethacin by novel ocular drug carriers
Improved ocular bioavailability of indomethacin by novel ocular drug carriers
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DOI：
10.1111/j.2042-7158.1996.tb03911.x
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发表时间：
1996-11-01
影响因子：
3.3
通讯作者：
Robinson, JR
中科院分区：
文献类型：
--
作者：
Calvo, P;Alonso, MJ;Robinson, JR
在兔眼中研究了不同药物载体提高药物眼部生物利用度的能力。所检测的药物载体为聚己内酯（PECL）制成的纳米颗粒、纳米胶囊和微米颗粒的悬浮液以及亚微米乳液。结果表明，纳米颗粒、纳米胶囊和乳液这三种亚微米系统使角膜、房水和虹膜睫状体中的吲哚美辛浓度增加了3倍以上 滴注后 0.5 小时和 1 小时。此外，与商业溶液获得的值相比，滴注亚微米系统后观察到吲哚美辛眼部生物利用度增加了 300%。相反，微粒几乎没有增加吲哚美辛的眼部生物利用度。通过共焦激光扫描显微镜研究了胶体载体与角膜上皮相互作用的机制。共焦图像表明亚微米颗粒通过内吞机制渗入角膜上皮细胞。三种胶体载体的相似行为表明它们的任何特定成分（PECL、卵磷脂和油）都充当渗透促进剂或内吞刺激剂。另一方面，当吲哚美辛封装在胶体载体中而不是微粒中时，其良好的眼部渗透性使我们假设这些载体的胶体性质是增加吲哚美辛眼部生物利用度的主要因素。PECL纳米颗粒和纳米胶囊以及亚微米乳液被证明是新型的角膜药物载体，因此代表了一种有用的方法 增加药物的眼部生物利用度。
The ability of different drug carriers to improve the ocular bioavailability of drugs was investigated in the rabbit eye. The assayed drug carriers were suspensions of nanoparticles, nanocapsules and microparticles made of poly-epsilon-caprolactone (PECL) and a submicron emulsion.Results indicated that the three submicron systems, nanoparticles, nanocapsules and emulsion, increased more than 3-fold the indomethacin concentration in the cornea, aqueous humour and iris-ciliary body at 0.5 and 1 h post-instillation. Furthermore, an increased indomethacin ocular bioavailability of 300% was observed after instillation of the submicron systems in comparison with the value obtained for a commercial solution. In contrast, the microparticles hardly increased the ocular bioavailability of indomethacin. The mechanism of interaction of the colloidal carriers with the corneal epithelium was investigated by confocal laser scanning microscopy. Confocal images indicated that submicron particles penetrate into the corneal epithelium cells by an endocytic mechanism. The similar behaviour of the three colloidal carriers suggests that any of their specific ingredients (PECL, lecithin and oil) acts as a penetration enhancer or an endocytotic stimulator. On the other hand, the favourable ocular penetration of indomethacin when encapsulated in the colloidal carriers, but not in the microparticles, led us to assume that the colloidal nature of these carriers is the main factor responsible for the increased ocular bioavailability of indomethacin.PECL nanoparticles and nanocapsules as well as submicron emulsions are shown to be novel corneal drug carriers, thus representing a useful approach for increasing the ocular bioavailability of drugs.