Drug Delivery & Nanomedicine Research Group; Public Health & Environmental Sustainability Research Group, Department of Pharmaceutics, University of Nigeria, Nsukka, Enugu State, Nigeria.
Department of Drug Delivery, HIPS - Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany.
Drug Deliv Transl Res. 2021 Aug;11(4):1655-1674. doi: 10.1007/s13346-021-00951-4. Epub 2021 Mar 19.
Artemether (ART) is second to artesunate in being the most widely used derivatives of artemisinin in combination therapy of malaria. Nanostructured lipid carrier (NLC) formulations were prepared following our previous report using optimized ART concentration of 0.25 g dissolved in 5% w/v mixture of solid (Gelucire 43/01 and Phospholipon 85G) and liquid (Transcutol) lipids at 90 °C. An aqueous surfactant phase at 90 °C was added (dropwise) under magnetic stirring (1000 rpm) for 5 min. The pre-emulsion was speedily homogenized at 28,000 rpm for 15 min and further probe sonicated at 60% amplitude (15 min). Resultant sample was cooled at room temperature and frozen at - 80 °C prior to lyophilization. The freeze-dried sample was used for solid-state characterization as well as in the formulation of transdermal nanogels using three polymers (Carbopol 971P, Poloxamer 407, and Prosopis africana peel powder) to embed the ART-NLC, using ethanol as a penetration enhancer. Transdermal ART-nanogels were characterized accordingly (physical examination, pH, drug content, rheology, spreadability, stability, particle size and morphology, skin irritation, in vitro and ex vivo skin permeation, and analysis of permeation data), P < 0.05. Results indicated that ART nanogels showed good encapsulation, drug release, pH-dependent swelling, stability, and tolerability. Overall, ART nanogels prepared from Poloxamer 407 showed the most desirable drug permeation, pH, swellability, spreadability, viscosity, and transdermal antiplasmodial properties superior to PAPP-ANG > C971P-ANG. A two-patch/week concurrent application of the studied nanogels could offer 100% cure of malaria as a lower-dose (50 mg ART) patient-friendly regimen devoid of the drug's many side effects.
青蒿琥酯（ART）是继青蒿素琥酯之后在疟疾联合治疗中应用最广泛的青蒿素衍生物。纳米结构脂质载体（NLC）制剂是根据我们之前的报告制备的，使用优化的 ART 浓度为 0.25g，溶解在 5%w/v 的固体（Gelucire 43/01 和 Phospholipon 85G）和液体（Transcutol）脂质混合物中，在 90°C。在磁力搅拌（1000rpm）下以 5min 滴加方式加入 90°C 的水相表面活性剂。将预乳液以 28000rpm 的速度快速匀浆 15min，然后以 60%的振幅进行探针超声处理（15min）。所得样品在室温下冷却，在-80°C 冷冻，然后进行冷冻干燥。冷冻干燥样品用于固态特性分析，以及使用三种聚合物（Carbopol 971P、泊洛沙姆 407 和非洲刺槐果皮粉）制备经皮纳米凝胶，使用乙醇作为渗透增强剂包埋 ART-NLC。经皮 ART-纳米凝胶相应地进行了特征描述（物理检查、pH 值、药物含量、流变学、铺展性、稳定性、粒径和形态、皮肤刺激性、体外和离体皮肤渗透以及渗透数据分析），P<0.05。结果表明，ART 纳米凝胶具有良好的包封、药物释放、pH 依赖性肿胀、稳定性和耐受性。总的来说，由泊洛沙姆 407 制备的 ART 纳米凝胶显示出最理想的药物渗透、pH 值、肿胀性、铺展性、粘度和经皮抗疟特性，优于 PAPP-ANG> C971P-ANG。每周使用两片/次研究的纳米凝胶可以提供 100%的疟疾治愈率，作为一种低剂量（50mgART）的患者友好型方案，没有药物的许多副作用。
