Lipid-based nanocarrier efficiently delivers highly water soluble drug across the blood–brain barrier into brain

Delivering highly water soluble drugs across blood–brain barrier (BBB) is a crucial challenge for the formulation scientists. A successful therapeutic intervention by developing a suitable drug delivery system may revolutionize treatment across BBB. Efforts were given here to unravel the capability of a newly developed fatty acid combination (stearic acid:oleic acid:palmitic acid = 8.08:4.13:1) (ML) as fundamental component of nanocarrier to deliver highly water soluble zidovudine (AZT) as a model drug into brain across BBB. A comparison was made with an experimentally developed standard phospholipid-based nanocarrier containing AZT. Both the formulations had nanosize spherical unilamellar vesicular structure with highly negative zeta potential along with sustained drug release profiles. Gamma scintigraphic images showed both the radiolabeled formulations successfully crossed BBB, but longer retention in brain was observed for ML-based formulation (MGF) as compared to soya lecithin (SL)-based drug carrier (SYF). Plasma and brain pharmacokinetic data showed less clearance, prolonged residence time, more bioavailability and sustained release of AZT from MGF in rats compared to those data of the rats treated with SYF/AZT suspension. Thus, ML may be utilized to successfully develop drug nanocarrier to deliver drug into brain across BBB, in a sustained manner for a prolong period of time and may provide an effective therapeutic strategy for many diseases of brain. Further, many anti-HIV drugs cannot cross BBB sufficiently. Hence, the developed formulation may be a suitable option to carry those drugs into brain for better therapeutic management of HIV.

将高水溶性药物穿透血脑屏障（blood–brain barrier, BBB），是制剂科学家面临的核心挑战。开发适配的药物递送系统以实现成功的治疗干预，或将彻底革新血脑屏障相关疾病的治疗范式。本研究旨在阐明一种新开发的脂肪酸组合物（硬脂酸:油酸:棕榈酸=8.08:4.13:1，记为ML）作为纳米载体基础组分，将高水溶性模型药物齐多夫定（zidovudine, AZT）经血脑屏障递送至脑部的能力。研究同时以实验构建的含AZT的标准磷脂基纳米载体作为对照。两种制剂均为纳米级球形单室囊泡结构，兼具高负ζ电位（zeta potential）与持续释药特性。γ闪烁显像图像显示，两种放射性标记制剂均可成功穿透血脑屏障，但基于ML的制剂（记为MGF）在脑部的滞留时长显著长于大豆卵磷脂（soya lecithin, SL）基药物载体（记为SYF）。血浆与脑部药代动力学数据表明，与SYF/AZT混悬液处理组大鼠相比，MGF组大鼠体内AZT的清除率更低、滞留时间更长、生物利用度更高，且释药更为持久。综上，ML可用于开发高效的药物纳米载体，以持续、长效的方式将药物经血脑屏障递送至脑部，为多种脑部疾病提供有效的治疗策略。此外，多数抗HIV药物无法有效穿透血脑屏障，因此本研究开发的制剂或可成为将此类药物递送至脑部、实现更优化HIV治疗管理的适宜方案。