Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nanoemulsion formulations were designed for enhancing the oral bioavailability of hydrophobic drugs. Paclitaxel was selected as a model hydrophobic drug, which is also a substrate for the P-glycoprotein efflux system. The oil-in-water (o/w) nanoemulsions were formulated with pine nut oil as the internal oil phase, egg lecithin as the primary emulsifier, and water as the external phase. Stearylamine and deoxycholic acid were used to impart positive and negative charge to the emulsions, respectively. Nanoemulsions were prepared by sonication method and characterized for particle size and surface charge. The control and nanoemulsion formulations with tritiated [3H]-paclitaxel were administered orally to female C57BL/6 mice and the distribution of the drug was examined. The formulated nanoemulsions had a particle size range of approximately 90-120 nm (laser diffraction method) and zeta potential values ranging from -56 mV to +34 mV. Following oral administration, a significantly higher concentration of paclitaxel was observed in the systemic circulation when administered in the nanoemulsion relative to control aqueous solution. The absorbed drug was found to be distributed in the liver, kidneys, and lungs. The results of this study suggest that nanoemulsions are promising novel formulations that can enhance the oral bioavailability of hydrophobic drugs, like paclitaxel.
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PMID:Improved oral delivery of paclitaxel following administration in nanoemulsion formulations. 1704 39

Indinavir, an antiretroviral protease inhibitor used in treatment of HIV infection has limited penetration into brain due to efflux of P-glycoprotein. The aim of this work was to develop transferrin coupled submicron lipid emulsions (SLEs) containing indinavir for delivery to brain. Stearylamine containing SLEs were prepared, characterized, tested for stability and optimized formulation (SLE-4) was developed. Transferrin was coupled to get SLE-6 by water soluble EDC method and purified by gel filtration. The coupled transferrin was quantified by modified Bradford dye assay method. The fluorescent dye (DiD oil) incorporated SLEs were used to check the brain specific delivery of SLEs. The in vivo pharmacokinetic and tissue distribution were conducted in mice. During pharmacokinetic studies, there was no significant difference in the serum levels of indinavir from SLE-1, SLE-4 and SLE-6 formulations at all time points. In tissue distribution studies the therapeutic availability (TA) of indinavir in brain from SLE-6 was 4.69, 3.1 and 1.7 times higher than drug solution, SLE-1 and SLE-4 respectively whereas, the TA of indinavir from SLE-4 was 2.76 and 1.82 times the drug solution and SLE-1. The brain to serum ratios with SLE-6 were above one indicates the brain specific delivery. The brain delivery of indinavir was improved with transferrin ligand attachment to SLEs by receptor mediated transcytosis.
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PMID:Brain delivery of transferrin coupled indinavir submicron lipid emulsions--pharmacokinetics and tissue distribution. 2156 69