Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo, Egypt.
Department of Industrial Pharmacy, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza, Egypt.
Drug Deliv. 2022 Dec;29(1):2549-2560. doi: 10.1080/10717544.2022.2100514.
It was found that propranolol hydrochloride (PNL), which is a beta-blocker used for hypertension treatment, has a potent spermicidal activity through local anesthetic activity or beta-blocking effect on sperm cells subsequently it could be used as a contraceptive remedy. This study aimed to entrap PNL into invasomes (INVs) and then formulate it as a locally acting contraceptive gel. PNL-loaded mucoadhesive INVs were prepared via the thin-film hydration technique. The D-optimal design was utilized to fabricate INVs employing lipid concentration (X), terpenes concentration (X), terpenes type (X), and chitosan concentration (X) as independent variables, while their impact was observed for entrapment efficiency percent (Y; EE%), particle size (Y; PS), zeta potential (Y; ZP), and amount of drug released after 6 h (Y; Q6h). Design Expert® was bestowed to nominate the desired formula. The selected INV was subjected to further studies and formulated into a mucoadhesive gel for and investigations. The optimum INV showed a spherical shape with EE% of 65.01 ± 1.24%, PS of 243.75 ± 8.13 nm, PDI of 0.203 ± 0.01, ZP of 49.80 ± 0.42 mV, and Q6h of 53.16 ± 0.73%. Differential scanning calorimetry study asserted the capability of INVs to entrap PNL. Permeation studies confirmed the desired sustained effect of PNL-loaded INVs-gel compared to PNL-gel, INVs, and PNL solution. Sperm motility assay proved the potency of INVs-gel to inhibit sperm motility. Besides, the histopathological investigation verified the tolerability of the prepared INVs-gel. Taken together, the gained data justified the efficacy of PNL-loaded INVs-gel as a potential locally acting contraceptive.
研究发现，盐酸普萘洛尔（PNL）作为一种用于高血压治疗的β受体阻滞剂，具有很强的杀精作用，通过对精子的局部麻醉作用或β阻断作用，因此可以作为一种避孕药物。本研究旨在将 PNL 包封到入侵小体（INV）中，然后将其制成局部作用的避孕凝胶。通过薄膜水化技术制备载有 PNL 的粘膜粘附 INV。采用 D-最优设计，以脂质浓度（X）、萜烯浓度（X）、萜烯类型（X）和壳聚糖浓度（X）为自变量，考察其对包封效率百分率（Y；EE%）、粒径（Y；PS）、Zeta 电位（Y；ZP）和 6 小时后药物释放量（Y；Q6h）的影响。Design Expert®软件被用来指定所需的配方。对选定的 INV 进行进一步研究，并将其制成粘膜粘附凝胶，进行 和 研究。最佳的 INV 呈球形，EE%为 65.01±1.24%，PS 为 243.75±8.13nm，PDI 为 0.203±0.01，ZP 为 49.80±0.42mV，Q6h 为 53.16±0.73%。差示扫描量热法研究表明 INV 能够包封 PNL。渗透研究证实，与 PNL 凝胶、INV 和 PNL 溶液相比，载 PNL 的 INV 凝胶具有理想的持续作用。精子运动性测定证明了 INV 凝胶抑制精子运动性的能力。此外，组织病理学研究证实了所制备的 INV 凝胶的耐受性。综上所述，载 PNL 的 INV 凝胶作为一种有潜力的局部作用避孕剂的疗效得到了数据的支持。
