Zein-alpha lipoic acid-loaded nanoparticles to enhance the oral bioavailability of dapoxetine: optimization and clinical pharmacokinetic evaluation

International Journal of Nanomedicine

关键词: Dapoxetine;    premature ejaculation;    mathematical experimental design;    nanoparticles;    clinical pharmacokinetics;    bioavailability.;   

DOI  :  

来源: DOAJ

【 摘 要 】

Khalid M El-Say,1,2 Osama AA Ahmed,1,3 Amir I Mohamed,4 Martin K Safo,5 Abdelsattar M Omar6,7 1Nanotechnology Laboratory, Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo 11651, Egypt; 3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt; 4Department of Pharmaceutics and Industrial Pharmacy, Military Medical Academy, Cairo, Egypt; 5Department of Medicinal Chemistry, and the Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA; 6Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; 7Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, EgyptCorrespondence: Khalid M El-SayPharmaceutics and Industrial Pharmacy, Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, P.O. Box: 80260, Jeddah, Saudi ArabiaTel [phone] 0073Fax [phone]Email [e-mail]: Premature ejaculation (PE) is the most common type of male sexual disorder with important psychological consequences. Dapoxetine (DPX), a recently approved drug for the treatment of PE, suffers from low bioavailability with large variability that ranges from 15–76% (mean 42%) after oral administration. The objective of this study is to optimize the parameters for the preparation of DPX-Zein-alpha lipoic acid (ALA) nanoparticles (NPs) to improve the bioavailability of DPX and consequently decrease therapeutic dose and adverse effect, leading to patient satisfaction and compliance.Methods: We investigated the effect of ALA concentration, PVA concentration and stirring rate on nanoparticle size (Y1), zeta potential (Y2), initial DPX release (Y3) and cumulative DPX release (Y4). In addition, in vivo pharmacokinetic study was performed for the optimized DPX formulation on human healthy volunteers compared with marketed DPX tablet.Results: The optimized DPX-loaded NPs showed Y1, Y2, Y3, and Y4 of 159.24 nm, 19.14 mV, 25.31% and 95.9 %, respectively. A single oral dose of 30 mg of optimized DPX-loaded NPs to human volunteers resulted in 2-fold improvement of AUC (1376.145±339.592 vs 709.178±146.307 in DPX), 4-fold increase in tmax (2.5±0.314 vs 0.583±0.144), prolongation of MRT (7.637±1.373 compared to 6.031±1.826 h), but with reduction in t1/2 (5.283±1.077 vs 8.452±2.813).Conclusion: The clinical findings suggest 194% enhancement of relative bioavailability of the optimized DPX-loaded NPs, potentially leading to a decrease in therapeutic dose and associated side effects in the treatment of PE.Keywords: dapoxetine, premature ejaculation, mathematical experimental design, nanoparticles, clinical pharmacokinetics, bioavailability

【 授权许可】

Unknown