Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt; Assiut International Center of Nanomedicine, Al-Rajhy Liver Hospital, Assiut University, Assiut 71515, Egypt.
Science Academy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt; Misr University for Science and Technology, 6th of October City 12566, Egypt.
Int J Pharm. 2021 Apr 1;598:120380. doi: 10.1016/j.ijpharm.2021.120380. Epub 2021 Feb 17.
Blindness and impaired vision are considered as the most troublesome health conditions leading to significant socioeconomic strains. The current study focuses on development of nanoparticulate systems (i.e., niosomes) as drug vehicles to enhance the ocular availability of betaxolol hydrochloride for management of glaucoma. Betaxolol-loaded niosomes were further laden into pH-responsive in situ forming gels to further extend precorneal retention of the drug. The niosomes were evaluated in terms of vesicle size, morphology, size distribution, surface charge and encapsulation efficiency. The optimized niosomes, comprised of Span® 40 and cholesterol at a molar ratio of 4:1, displayed particle size of 332 ± 7 nm, zeta potential of -46 ± 1 mV, and encapsulation efficiency of 69 ± 5%. The optimal nanodispersion was then incorporated into a pH-triggered in situ forming gel comprised of Carbopol® 934P and hydroxyethyl cellulose. The formed gels were translucent, pseudoplastic, mucoadhesive, and displayed a sustained in vitro drug release pattern. Upon instillation of the betaxolol-loaded niosomal gel into rabbits' eyes, a prolonged intraocular pressure reduction and significant enhancement in the relative bioavailability of betaxolol (280 and 254.7%) in normal and glaucomatous rabbits, were attained compared to the marketed eye drops, respectively. Hence, the developed pH-triggered nanoparticulate gelling system might provide a promising carrier for ophthalmic drug delivery and for improved augmentation of glaucoma.
失明和视力障碍被认为是导致重大社会经济负担的最麻烦的健康状况。本研究专注于开发纳米颗粒系统（即囊泡）作为药物载体，以提高盐酸倍他洛尔的眼部可用性，用于治疗青光眼。载有盐酸倍他洛尔的囊泡进一步载入 pH 响应原位形成凝胶中，以进一步延长药物在角膜前的滞留时间。囊泡的评价指标包括囊泡大小、形态、粒径分布、表面电荷和包封效率。优化的囊泡由摩尔比为 4:1 的 Span® 40 和胆固醇组成，粒径为 332±7nm，zeta 电位为-46±1mV，包封效率为 69±5%。然后，将最佳纳米分散体掺入由 Carbopol® 934P 和羟乙基纤维素组成的 pH 触发原位形成凝胶中。形成的凝胶为半透明、假塑性、粘膜粘附性，并呈现出持续的体外药物释放模式。与市售滴眼剂相比，将载有盐酸倍他洛尔的囊泡凝胶滴入兔子眼睛后，可延长眼压降低时间，并显著提高正常和青光眼兔子中盐酸倍他洛尔的相对生物利用度（分别为 280%和 254.7%）。因此，开发的 pH 触发纳米颗粒胶凝系统可能为眼部药物递送提供有前途的载体，并改善青光眼的治疗效果。
