Fang Guihua, Zhao Rongrong, Zhu Lu, Wang Qiuxiang, Peng Sifan, Kang Lihua, Lu Hong, Zhang Guowei, Tang Bo
School of Pharmacy, Nantong University, Nantong, Jiangsu Province 226001, China.
Eye Institute, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, China.
J Control Release. 2025 Mar 10;379:14-29. doi: 10.1016/j.jconrel.2024.12.075. Epub 2025 Jan 16.
Corneal inflammation, a condition that can potentially lead to blindness, is often treated with topical eye drops. However, the limited ocular drug bioavailability of the eye drops necessitates frequent dosing. Herein, a nanoemulsion-based pseudopolyrotaxane hydrogel was fabricated to improve corneal bioavailability and thereby suppress inflammation. In this approach, dexamethasone was encapsulated into a nanoemulsion emulsified by Tween 80. The nanoemulsion was then mixed with γ-Cyclodextrin (γ-CD) aqueous solution to produce dexamethasone-loaded nanoemulsion-based pseudopolyrotaxane hydrogel (DEX-NPH) via host-guest interaction between Tween 80 and γ-CD. The hydrogel exhibited a shear-thinning and thixotropy character. In vitro drug release and hydrogel dissolution studies showed that drugs released from hydrogel predominantly in the form of nanoemulsion. The ocular surface fluorescence imaging and tear pharmacokinetics indicated that the hydrogel could significantly prolong precorneal residence time. The corneal pharmacokinetics suggested that DEX-NPH with 35 % γ-CD improved corneal bioavailability by 1.29-fold compared with nanoemulsion and by 4.09-fold compared with free drug solution. In particular, the precorneal retention capacity and corneal bioavailability could be adjusted by changing the γ-CD content in the hydrogel. Moreover, ocular irritation evaluation confirmed the excellent safety of such hydrogel. In an alkali burn-induced corneal inflammation model, the hydrogel exhibited a superior anti-inflammatory effect compared to nanoemulsion or free drug solution alone. In summary, the nanoemulsion-based pseudopolyrotaxane hydrogel is promising for enhancing corneal bioavailability and treating corneal inflammation.
角膜炎症是一种可能导致失明的病症，通常采用局部滴眼液进行治疗。然而，滴眼液有限的眼部药物生物利用度需要频繁给药。在此，制备了一种基于纳米乳液的假聚轮烷水凝胶，以提高角膜生物利用度，从而抑制炎症。在这种方法中，地塞米松被包裹在由吐温80乳化的纳米乳液中。然后将纳米乳液与γ-环糊精（γ-CD）水溶液混合，通过吐温80与γ-CD之间的主客体相互作用，制备出负载地塞米松的基于纳米乳液的假聚轮烷水凝胶（DEX-NPH）。该水凝胶表现出剪切变稀和触变性特征。体外药物释放和水凝胶溶解研究表明，药物主要以纳米乳液的形式从水凝胶中释放。眼表荧光成像和泪液药代动力学表明，该水凝胶可显著延长角膜前滞留时间。角膜药代动力学表明，含35%γ-CD的DEX-NPH与纳米乳液相比，角膜生物利用度提高了1.29倍，与游离药物溶液相比提高了4.09倍。特别是，角膜前滞留能力和角膜生物利用度可通过改变水凝胶中γ-CD的含量来调节。此外，眼部刺激性评估证实了这种水凝胶具有出色的安全性。在碱烧伤诱导的角膜炎症模型中，该水凝胶与单独的纳米乳液或游离药物溶液相比，表现出优异的抗炎效果。总之，基于纳米乳液的假聚轮烷水凝胶在提高角膜生物利用度和治疗角膜炎症方面具有广阔前景。
