title: In-situ single pass intestinal permeability and pharmacokinetic study of developed Lumefantrine loaded solid lipid nanoparticles.
abstract: 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±43.27nm, 25.29±1.15mV 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±521ng/mL and 43181±2557h×ng/mL, respectively) as compared to that of LF-control suspension (1425±563ng/mL and 19586±1537h×ng/mL, respectively). Thus, developed LF-SLNs can be promising to overcome P-gp efflux pump and enhance the oral bioavailability of lumefantrine.
authors.affiliation: National Institute of Pharmaceutical Education and Research (NIPER), ITI Compound, Raebareli, Uttar Pradesh, India.
authors.forename: Anuj
authors.initials: A
authors.lastname: Garg
authors.affiliation: National Institute of Pharmaceutical Education and Research (NIPER), ITI Compound, Raebareli, Uttar Pradesh, India.
authors.forename: Kripal
authors.initials: K
authors.lastname: Bhalala
authors.affiliation: National Institute of Pharmaceutical Education and Research (NIPER), ITI Compound, Raebareli, Uttar Pradesh, India.
authors.forename: Devendra Singh
authors.initials: DS
authors.lastname: Tomar
authors.affiliation: National Institute of Pharmaceutical Education and Research (NIPER), ITI Compound, Raebareli, Uttar Pradesh, India; Division of Pharmacokinetics & Metabolism, CSIR-Central Drug Research Institute (CDRI), Lucknow, Uttar Pradesh, India. Electronic address: wahajuddin@cdri.res.in.
authors.lastname: Wahajuddin
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D003460:Crystallization; D004983:Ethanolamines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005449:Fluorenes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D008055:Lipids / Q000737:chemistry*; D000078102:Lumefantrine; D008297:Male; D051379:Mice; D053758:Nanoparticles; D010316:Particle Size; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000962:Antimalarials; D004983:Ethanolamines; D005449:Fluorenes; D008055:Lipids; D000078102:Lumefantrine
keywords: In situ single pass intestinal permeability study (SPIP); Intestinal permeability; Lumefantrine; Oral bioavailability; P-glycoprotein pump efflux; Solid lipid nanoparticle