Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October 6 University, Central Axis, 6th of October City, Giza, 12585, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
Daru. 2020 Dec;28(2):517-532. doi: 10.1007/s40199-020-00355-8. Epub 2020 Jun 20.
Adefovir dipivoxil (AD), a nucleoside reverse transcriptase inhibitor is effective against Hepatitis B virus. Its poor oral bioavailability leads to frequent administration causing severe adverse effects. Thereby the entrapment of AD within lipid nanoparticulate systems is a way of increasing AD oral bioavailability as a result of improving intestinal permeability with efficient liver-targeted delivery together with higher drug stability during storage.
AD-loaded nanostructured lipid carriers (AD-NLCs) were prepared via solvent emulsification diffusion technique adopting 2 full factorial design to study the effect of lipid percentage, presence of egg yolk lecithin, surfactant type and percentage on entrapment efficiency (E.E.%), particle size and percent in-vitro drug released after 8 h (Q8hrs).
Formula (F12) showed E.E.% of 90.5 ± 0.2%, vesicle size of 240.2 ± 2.5 nm and Q8hrs of 58.55 ± 9.4% was selected as the optimum formula with desirability value of 0.757 based on highest EE%, lowest P.S. and Q8hrs. Further evaluation of the optimized formula using radioiodinated rose bengal (RIRB) in thioacetamide induced liver damage in Swiss Albino mice revealed a higher liver uptake of 22 ± 0.01% ID/g (percent injected dose/g organ) and liver uptake/Blood (T/B) ratio of 2.22 ± 0.067 post 2 h of I.V injection of RIRB compared to 9 ± 0.01% ID/g and 0.64 ± 0.017 in untreated group, respectively.
NLCs could be successfully used as oral drug delivery carriers of the antiviral drug Adefovir Dipivoxil to the liver with higher stability and oral bioavailability. Graphical abstract.
阿德福韦酯（AD）是一种核苷类逆转录酶抑制剂，对乙型肝炎病毒有效。但其口服生物利用度差，导致频繁给药，引起严重的不良反应。因此，将 AD 包封在脂质纳米颗粒系统中是一种提高 AD 口服生物利用度的方法，通过提高肠道通透性，实现有效的肝靶向递送，同时在储存过程中提高药物稳定性。
采用溶剂乳化扩散技术制备载有阿德福韦酯的纳米结构脂质载体（AD-NLCs），采用 2 因素完全实验设计研究脂质百分比、蛋黄卵磷脂的存在、表面活性剂类型和百分比对包封效率（E.E.%）、粒径和 8 小时后体外药物释放百分比（Q8hrs）的影响。
配方（F12）的 E.E.%为 90.5±0.2%，囊泡粒径为 240.2±2.5nm，Q8hrs 为 58.55±9.4%，选择最佳配方，基于最高 EE%、最低 P.S.和 Q8hrs，其理想性值为 0.757。进一步使用放射性碘标记玫瑰红（RIRB）在硫代乙酰胺诱导的瑞士白化病小鼠肝损伤模型中评价优化配方，发现静脉注射 RIRB 后 2 小时，肝摄取率为 22±0.01% ID/g（注射剂量/g 器官），肝摄取/血（T/B）比值为 2.22±0.067，而未治疗组分别为 9±0.01% ID/g 和 0.64±0.017。
NLCs 可成功用作抗病毒药物阿德福韦酯的口服药物递送载体，具有更高的稳定性和口服生物利用度。
