In-situ single pass intestinal permeability and pharmacokinetic study of developed Lumefantrine loaded solid lipid nanoparticles
| Autor: | Kripal Bhalala, Wahajuddin, Anuj Garg, Devendra Singh Tomar |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
Pharmaceutical Science Administration Oral Biological Availability 02 engineering and technology Polyethylene glycol Lumefantrine 030226 pharmacology & pharmacy Permeability Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Antimalarials Mice 0302 clinical medicine Solid lipid nanoparticle Zeta potential Animals ATP Binding Cassette Transporter Subfamily B Member 1 Particle Size Fluorenes Chromatography Calorimetry Differential Scanning Caprylic acid Poloxamer 021001 nanoscience & nanotechnology Lipids Bioavailability Rats chemistry Intestinal Absorption Solubility Ethanolamines Area Under Curve Nanoparticles Stearic acid 0210 nano-technology Crystallization |
| Zdroj: | International journal of pharmaceutics. 516(1-2) |
| ISSN: | 1873-3476 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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