Prabhu Priyanka, Suryavanshi Shital, Pathak Sulabha, Patra Aditya, Sharma Shobhona, Patravale Vandana
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai 400019, Maharashtra, India.
Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005, Maharashtra, India.
Int J Pharm. 2016 Nov 20;513(1-2):504-517. doi: 10.1016/j.ijpharm.2016.09.008. Epub 2016 Sep 3.
Patients with cerebral malaria (CM) are unable to take oral medication due to impaired consciousness and vomiting thus necessitating parenteral therapy. Quinine, artemether, and artesunate which are currently used for parenteral malaria therapy have their own drawbacks. The World Health Organization (WHO) has now banned monotherapy and recommends artemisinin-based combination therapy for malaria treatment. However, presently there is no intravenous formulation available for combination therapy of malaria. Artemether-Lumefantrine (ARM-LFN) is a WHO approved combination for oral malaria therapy. However, the low aqueous solubility of ARM and LFN hinders their intravenous delivery. The objective of this study was to formulate ARM-LFN nanostructured lipid carriers (NLC) for intravenous therapy of CM. ARM-LFN NLC were prepared by microemulsion template technique and characterized for size, drug content, entrapment efficiency, drug release, crystallinity, morphology, amenability to autoclaving, compatibility with infusion fluids, stability, antimalarial efficacy in mice, and toxicity in rats. The ARM-LFN NLC showed sustained drug release, amenability to autoclaving, compatibility with infusion fluids, good stability, complete parasite clearance and reversal of CM symptoms with 100% survival in Plasmodium berghei-infected mice, and safety in rats. The biocompatible ARM-LFN NLC fabricated by an industrially feasible technique offer a promising solution for intravenous therapy of CM.
脑型疟疾（CM）患者由于意识障碍和呕吐而无法口服药物，因此需要进行肠胃外治疗。目前用于肠胃外疟疾治疗的奎宁、蒿甲醚和青蒿琥酯都有各自的缺点。世界卫生组织（WHO）现已禁止单一疗法，并推荐以青蒿素为基础的联合疗法用于疟疾治疗。然而，目前尚无用于疟疾联合治疗的静脉制剂。蒿甲醚-本芴醇（ARM-LFN）是WHO批准的用于口服疟疾治疗的联合用药。然而，ARM和LFN的低水溶性阻碍了它们的静脉给药。本研究的目的是制备用于CM静脉治疗的ARM-LFN纳米结构脂质载体（NLC）。通过微乳模板技术制备ARM-LFN NLC，并对其粒径、药物含量、包封率、药物释放、结晶度、形态、耐高压灭菌性、与输液的相容性、稳定性、对小鼠的抗疟疗效以及对大鼠的毒性进行表征。ARM-LFN NLC显示出持续的药物释放、耐高压灭菌性、与输液的相容性、良好的稳定性、完全清除寄生虫以及在感染伯氏疟原虫的小鼠中使CM症状逆转且生存率达100%，并且在大鼠中具有安全性。通过工业上可行的技术制备的具有生物相容性的ARM-LFN NLC为CM的静脉治疗提供了一种有前景的解决方案。
