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

Abstract

BackgroundPremature 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.MethodsWe 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.ResultsThe 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).ConclusionThe 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.

<p>Pumpkin Oil–Based Nanostructured Lipid Carrier System for Antiulcer Effect in NSAID-Induced Gastric Ulcer Model in Rats</p>

“…44 The important criteria for efficacy and efficiency of nanoparticles (drug release, biodistribution and cellular uptake) are particle size and size distribution. 46,47 Table 1 shows the PSO-NLCs size variabilities for the prepared formulations. The results revealed that the size ranged from 65.0 to 284.0 nm for formulations F13 and F14, respectively.…”

Influence of the Dispersion Medium and Cryoprotectants on the Physico-Chemical Features of Gliadin- and Zein-Based Nanoparticles

“…Namely, their use as cryoprotectants endows several advantages such as Maillard browning reactions, particularly detrimental to protein-based nanoformulations, as recently demonstrated for Brij O10-stabilized zein nanoparticles [36]. Moreover, the absence of internal hydrogen bonds enhances the interaction of these cryoprotectants with the carriers, as is true for other nanosystems such as chitosan- [63,64] and zein-based nanoparticles proposed for the oral delivery of dapoxetine and resveratrol [65,66]. In fact, trehalose and sucrose have already demonstrated themselves to be particularly suitable for stabilizing protein-based nanoparticles made up of human serum albumin [67].…”

Two-Step Optimization to Develop a Transdermal Film Loaded With Dapoxetine Nanoparticles: A Promising Technique to Improve Drug Skin Permeation

“…They reported an increase in the relative bioavailability by 194% from the prepared formulation when compared to the marketed drug product. 48 In this study, the prepared DPX PNPs formulation is similar to the abovementioned NPs in terms of size and drug load. Our optimized transdermal film loaded with DPX PNPs could be considered as a superior DPX drug delivery system due to avoiding of the drug first-pass effect from the transdermal route.…”