In-situ single pass intestinal permeability and pharmacokinetic study of developed Lumefantrine loaded solid lipid nanoparticles

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• 作者：Anuj Garg^a ; ¹ ; Kripal Bhalala^a ; ¹ ; Devendra Singh Tomar^a ; Wahajuddin^a ; ^b ; ^{wahajuddin@cdri.res.in} ; ^{wahajuddin@gmail.com}
• 关键词：Lumefantrine ; Solid lipid nanoparticle ; P-glycoprotein pump efflux ; Intestinal permeability ; Oral bioavailability ; In situ single pass intestinal permeability study (SPIP)
• 刊名：International Journal of Pharmaceutics
• 出版年：2017
• 出版时间：10 January 2017
• 年：2017
• 卷：516
• 期：1-2
• 页码：120-130
• 全文大小：1368 K
• 卷排序：516

文摘

The present investigation aims to develop lumefantrine loaded binary solid lipid nanoparticles (LF-SLNs) to improve its poor and variable oral bioavailability. The oral bioavailability of LF is poor and variable due to its limited aqueous solubility and P-gp mediated efflux occurring in small intestine. LF-SLNs were prepared using binary lipid mixture of stearic acid and caprylic acid stabilized with TPGS (D-alpha tocopheryl polyethylene glycol 1000 succinate) and Poloxamer 188. Developed LF-SLNs were characterized for particle size distribution, zeta potential, entrapment efficiency, solid state properties and biopharmaceutical properties including in situ intestinal permeability and oral bioavailability. The particle size distribution, zeta potential and entrapment efficiency of optimized batch (LF-SLN7) was found to be 357.7 ± 43.27 nm, 25.29 ± 1.15 mV and 97.35 ± 0.30%, respectively. DSC thermographs showed loss of crystalline nature of lumefantrine in LF-SLNs. In situ single pass intestinal permeability study (SPIP) study indicated significant enhancement in the effective intestinal permeability of LF from LF-SLN7 as compared to that of control. Pharmacokinetic study also showed significant increase in Cmax and area under curve (AUC0-∞) from LF-SLN7 (3860 ± 521 ng/mL and 43181 ± 2557 h × ng/mL, respectively) as compared to that of LF-control suspension (1425 ± 563 ng/mL and 19586 ± 1537 h × ng/mL, respectively). Thus, developed LF-SLNs can be promising to overcome P-gp efflux pump and enhance the oral bioavailability of lumefantrine.