Purpose

Lumefantrine (LF) is an antimalarial agent with low water solubility and inconsistent oral bioavailability (4–11%), which limits its therapeutic potential. Hence, this research aimed to design nanostructured lipid carriers (NLCs) for LF to improve its oral administration.

Methods

LF-NLCs were formulated using the hot emulsification-probe sonication method. Solubility and molecular interactions studies were performed for the selection of appropriate formulation excipients. Various critical formulation and process variables were optimized during this process. The optimized LF-NLC was then evaluated for various physicochemical properties. Ex vivo gut permeation was done to analyze LF-NLC permeation across the gut, and in vitro drug release was performed to understand its release behavior.

Results

Particle size, polydispersity index (PDI), zeta potential, and % encapsulation efficiency of the optimized formulation were found to be 78.85 ± 2.55 nm, 0.255 ± 0.03, -8.25 ± 2.29 mV, and 74.32 ± 1.63%, respectively. Transmission electron microscopy revealed the particulate nature and spherical shape of LF-NLCs. The loss of sharp endothermic peak in DSC and reduced crystallinity in XRD indicated the amorphization of encapsulated drug. The in vitro drug release study showed sustained release of LF from NLC. Ex vivo gut permeation exhibited an almost 3.5-fold increase in permeation of NLCs over plain drug suspension.

Conclusion

According to the above findings, NLC could be a promising approach for the oral delivery of LF and drugs with similar properties.

中文翻译：

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具有增强渗透性的 Lumefantrine 的纳米结构脂质载体 (NLC)

目的

Lumefantrine (LF) 是一种抗疟药，具有低水溶性和不一致的口服生物利用度（4-11%），这限制了其治疗潜力。因此，本研究旨在设计用于 LF 的纳米结构脂质载体 (NLC) 以改善其口服给药。

方法

LF-NLC 使用热乳化-探针超声法配制。进行溶解度和分子相互作用研究以选择合适的制剂赋形剂。在此过程中优化了各种关键配方和工艺变量。然后评估优化的 LF-NLC 的各种物理化学性质。进行体外肠道渗透以分析整个肠道的 LF-NLC 渗透，并进行体外药物释放以了解其释放行为。

结果

发现优化配方的粒径、多分散指数 (PDI)、zeta 电位和% 包封效率分别为 78.85 ± 2.55 nm、0.255 ± 0.03、-8.25 ± 2.29 mV 和 74.32 ± 1.63%。透射电子显微镜揭示了 LF-NLC 的颗粒性质和球形。DSC 中尖锐吸热峰的消失和 XRD 中结晶度的降低表明包封药物的非晶化。体外药物释放研究表明 LF 从 NLC 中持续释放。离体肠道渗透显示 NLC 的渗透率比普通药物悬浮液增加了近 3.5 倍。

结论

根据上述发现，NLC 可能是口服给药 LF 和具有相似特性的药物的一种有前途的方法。