Abstract

The aim of this research was the development and optimization of nanoniosomes for delivery of glibenclamide (Gbn) as hypoglycaemic agent to the lung in an inhaler dosage form. Fifteen formulae of niosomal dispersions were prepared according to Box–Behnken design. The effect of drug amount, Cholesterol molar ratio, and Hydrophilic lipophilic balance (HLB) values of the surfactant on the mean vesicle size, Zeta potential (ZP), polydispersity index (PDI), entrapment efficiency, and in-vitro released of Gbn were investigated. A quality control check was performed on an inhaler filled with the optimum nanoniosomal formula. The in-vivo hypoglycaemic effect of nanoniosomal inhalation was also evaluated. The vesicle size observed of the optimized formula was 172 ± 4.6 nm, PDI was 0.304 ± 0.06 and ZP was −49.9 ± 1.5 mv with 69 ± 9.3% in-vitro drug release after 2 h. The Cholesterol molar ratio and the HLB value showed a statistically significant effect on dependent variables. In-vivo results proved that nanoniosomes were efficiently delivered from the inhalation canister showing a mass median aerodynamic diameter of 1.4 micron. The inhaled nanoniosomal dispersion loaded with Gbn showed a decrease in blood glucose level of hyperglycaemic rats by 51.42 ± 5.2%± after 180 min which was nearly two folds compared to oral Gbn. Gibenclamide nanoniosomes inhaler could be suggested as a novel effective dosage form for the treatment of Diabetes mellitus.

摘要

本研究的目的是开发和优化用于将格列本脲 (Gbn) 作为降血糖剂以吸入剂形式输送到肺部的纳米脂质体。根据 Box-Behnken 设计制备了 15 种 niosomal 分散体配方。药物用量、胆固醇摩尔比和表面活性剂的亲水亲油平衡 (HLB) 值对 Gbn的平均囊泡大小、Zeta 电位 (ZP)、多分散指数 (PDI)、包封率和体外释放的影响为调查。对装有最佳纳米糖体配方的吸入器进行质量控制检查。在体内还评估了纳米微粒体吸入的降血糖作用。观察到的优化配方的囊泡大小为 172 ± 4.6 nm，PDI 为 0.304 ± 0.06，ZP 为 -49.9 ± 1.5 mv，2 小时后体外药物释放率为 69 ± 9.3% 。胆固醇摩尔比和 HLB 值显示出对因变量的统计显着影响。体内结果证明纳米脂质体从吸入罐中有效递送，显示质量中值空气动力学直径为 1.4 微米。负载 Gbn 的吸入纳米糖体分散体显示，高血糖大鼠的血糖水平在 180 分钟后降低了 51.42 ± 5.2% ±，与口服 Gbn 相比几乎是两倍。吉本脲纳米脂质体吸入器可作为治疗糖尿病的新型有效剂型。