Suriyaamporn Phuvamin, Opanasopit Praneet, Rangsimawong Worranan, Ngawhirunpat Tanasait
Pharmaceutical Development of Green Innovations Group (PDGIG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.
Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani 34190, Thailand.
Pharmaceutics. 2022 Feb 22;14(3):472. doi: 10.3390/pharmaceutics14030472.
The optimal design of novel microneedles (MNs) for the ocular delivery system is necessary and useful for improving the effectiveness of medication. The objective of this study was to design and develop the optimal fluconazole (FLUZ)-microemulsions (MEs)-loaded two-layered dissolving MNs as a potential treatment for fungal eye infection. The experimental designs using the simplex-lattice design were used to select the optimal formulation. The two-layered dissolving MNs were fabricated from 3% chitosan and 20% polyvinyl alcohol (PVA) in a weight ratio of 1:4 as an outer layer and FLUZ-loaded MEs containing eugenol, tween 80, PEG400, and water as an inner layer. The physical appearance, mechanical properties, penetration ability, dissolution time, in vitro/ex vivo ocular drug delivery, and antifungal activity were evaluated. From the results, the optimal two-layered dissolving MNs exhibited good physical properties, complete insertion, minimally invasive ocular tissue, and high stability at 4 °C and 25 °C for 3 months. Moreover, the optimal two-layered dissolving MNs showed significantly higher FLUZ permeation into the ocular tissue than other formulations, while providing highly potential antifungal activity. In conclusion, the optimal MEs-loaded two-layered MNs' formulation had appropriate properties for ocular delivery of FLUZ, resulting in an improvement of fungal keratitis treatment.
新型微针用于眼部给药系统的优化设计对于提高药物疗效是必要且有用的。本研究的目的是设计并开发出最佳的载氟康唑（FLUZ）微乳（MEs）双层溶解微针，作为治疗真菌性眼部感染的潜在疗法。采用单纯形格子设计的实验方法来选择最佳配方。双层溶解微针以外层为按重量比1:4的3%壳聚糖和20%聚乙烯醇（PVA）制成，内层为含丁香酚、吐温80、聚乙二醇400和水的载FLUZ微乳。对其外观、机械性能、穿透能力、溶解时间、体内外眼部给药以及抗真菌活性进行了评估。结果表明，最佳双层溶解微针具有良好的物理性能、能完全插入、对眼部组织微创，且在4℃和25℃下3个月具有高稳定性。此外，最佳双层溶解微针显示出比其他配方更高的FLUZ渗透进入眼部组织的能力，同时具有高度潜在的抗真菌活性。总之，最佳载微乳双层微针配方具有适合FLUZ眼部给药的特性，从而改善了真菌性角膜炎的治疗效果。
