Kaul Shreya, Nagaich Upendra, Verma Navneet
Department of Pharmaceutics, Faculty of Pharmacy, IFTM University, Uttar Pradesh, Moradabad, India.
Department of Pharmaceutics, Amity Institute of Pharmacy, Amity University, Noida, India.
Drug Deliv Transl Res. 2022 Jul;12(7):1719-1737. doi: 10.1007/s13346-021-01072-8. Epub 2021 Sep 28.
The research work was driven to develop, optimize, and characterize novel nanostructured liquid crystalline particles as carriers for the ocular delivery of vancomycin. The formulations were developed by fragmenting the cubic crystalline phase of glycerol monooleate, water, and poloxamer 407. A four-factor, three-level Taguchi statistical experimental design was constructed to optimize the formulation. Formulations exhibited internal-cubic structure of the vesicles with particle size in the range of 51.11 ± 0.96 nm to 158.73 ± 0.46 nm and negative zeta potential. Ex vivo transcorneal permeation studies demonstrated that the optimized cubosomes had a 2.4-fold increase in apparent permeability co-efficient as compared to vancomycin solution, whereas in vivo studies in rabbits demonstrated that the severity of keratitis was considerably lowered on day 3 with optimized cubosomes. Ocular pharmacokinetic studies evaluated the level of drug in aqueous humor, and results revealed that the time to peak concentration (T) of vancomycin-loaded cubosomal formulation was about 1.9-fold higher and mean residence time was 2.2-fold greater than vancomycin solution. Furthermore, histological examination revealed that the corneal layers displayed well-maintained morphology without any stromal swelling, consequently indicating the safety of formulation. It could be concluded that the developed nanostructured liquid crystalline particles of vancomycin demonstrated improved pre-ocular residence time, increased permeability, reduced dosing frequency, controlled drug release, and reduced systemic side-effects. Results manifested that the developed vancomycin-loaded cubosomes could be a promising novel ocular carrier and an ideal substitute for conventional eye drops for the management of bacterial-keratitis.
该研究工作旨在开发、优化和表征新型纳米结构液晶颗粒，作为万古霉素眼部给药的载体。通过将单油酸甘油酯、水和泊洛沙姆407的立方晶相破碎来制备制剂。构建了一个四因素、三水平的田口统计实验设计来优化制剂。制剂表现出囊泡的内部立方结构，粒径范围为51.11±0.96nm至158.73±0.46nm，且zeta电位为负。离体角膜渗透研究表明，与万古霉素溶液相比，优化后的立方液晶纳米粒的表观渗透系数增加了2.4倍，而在兔体内研究表明，在第3天时，优化后的立方液晶纳米粒可显著降低角膜炎的严重程度。眼部药代动力学研究评估了房水中的药物水平，结果显示，载万古霉素立方液晶纳米粒制剂的达峰时间（T）约为万古霉素溶液的1.9倍，平均驻留时间为万古霉素溶液的2.2倍。此外，组织学检查显示角膜层形态保持良好，无任何基质肿胀，因此表明该制剂具有安全性。可以得出结论，所开发的万古霉素纳米结构液晶颗粒具有改善的眼表滞留时间、增加的渗透性、降低的给药频率、可控的药物释放和减少的全身副作用。结果表明，所开发的载万古霉素立方液晶纳米粒可能是一种有前途的新型眼部载体，是治疗细菌性角膜炎的传统眼药水的理想替代品。
