Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Egypt.
Int J Pharm. 2023 Sep 25;644:123338. doi: 10.1016/j.ijpharm.2023.123338. Epub 2023 Aug 20.
Migraine is a disabling neurovascular polygenic disorder affecting life quality with escorted socioeconomic encumbrances. Herein, we investigated the consolidated amalgamation of passive lipomer approach alongside active sonophoresis assisted transdermal delivery of zolmitriptan (ZT) using high frequency ultrasound pre-treatment protocol to mitigate migraine attacks. A modified nanoprecipitation technique was utilized to prepare zolmitriptan loaded lipomers (ZTL) adopting 2 factorial design. Three factors were scrutinized namely lipid type, ZT: lipid ratio and ZT: Gantrez® ratio. The prepared systems were characterized regarding particle size, zeta potential, polydispersity index, entrapment efficiency and in-vitro release studies. The best achieved ZTL system was evaluated for ZT- Gantrez® intermolecular interactions, drug crystallinity, morphology, ex-vivo permeation and histopathological examination. Finally, a comparative in-vivo biodistribution study through radiotracking technique using Technetium-99 m was adopted. L2 was the best-achieved ZTL system with respect to spherical particle size (390.7 nm), zeta-potential (-30.8 mV), PDI (0.2), entrapment efficiency (86.2%), controlled release profile, flux (147.13 μg/cm/hr) and enhancement ratio (5.67). Histopathological studies proved the safety of L2 system upon application on skin. L2 revealed higher brain C (12.21 %ID/g), prolonged brain MRT (8.67 hr), prolonged brain 0.23 hr), significantly high relative bioavailability (2929.36%) and similar brain T (0.5 hr) compared to I.V. route with higher brain/blood ratio. Thus, sonophoresis assisted transdermal delivery of ZTL offers a propitious alterative to alleviate migraine symptoms.
偏头痛是一种致残性的神经血管多基因疾病，会影响生活质量，并伴有伴社交经济负担。在此，我们研究了被动脂质体方法与高频超声预处理方案辅助下的主动声透皮递送佐米曲普坦（ZT）的综合联合应用，以减轻偏头痛发作。采用改进的纳米沉淀技术，采用 2 因素设计制备载有佐米曲普坦的脂质体（ZTL）。考察了 3 个因素，即脂质类型、ZT：脂质比和 ZT：Gantrez®比。对所制备的系统进行了粒径、zeta 电位、多分散指数、包封效率和体外释放研究。对最佳的 ZTL 系统进行了 ZT-Gantrez®分子间相互作用、药物结晶度、形态学、体外渗透和组织病理学检查。最后，采用放射性示踪技术通过锝-99m 进行了体内生物分布比较研究。L2 是在球形粒径（390.7nm）、zeta 电位（-30.8mV）、PDI（0.2）、包封效率（86.2%）、控制释放曲线、流量（147.13μg/cm/hr）和增强比（5.67）方面表现最佳的 ZTL 系统。组织病理学研究证明 L2 系统在皮肤应用时是安全的。L2 系统在脑中 C（12.21%ID/g）更高、脑 MRT（8.67 小时）延长、脑 0.23 小时）延长、相对生物利用度显著提高（2929.36%）和脑 T（0.5 小时）与静脉内途径相似，脑/血比更高。因此，佐米曲普坦经皮超声辅助递送提供了一种缓解偏头痛症状的有利替代方法。
