Self-assembled biodegradable polymeric micelles to improve dapoxetine delivery across the blood-brain barrier

• Published in: International journal of nanomedicine Vol. 13; pp. 3679 - 3687
• Main Authors: Abourehab, Mohammed As, Ahmed, Osama Aa, Balata, Gehan F, Almalki, Waleed H
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2018; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Analysis; Animals; Benzylamines - blood; Benzylamines - pharmacokinetics; Benzylamines - pharmacology; Bioavailability; Biocompatible Materials - chemistry; biodegradable copolymer; Biological Availability; Biological Transport - drug effects; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; brain delivery; Copolymers; Diffusion; Drug Carriers; Drug Delivery Systems; Electron microscopy; FDA approval; Fourier transforms; Humans; Infrared spectroscopy; Male; Micelles; Nanoparticles; Nanotechnology; Naphthalenes - blood; Naphthalenes - pharmacokinetics; Naphthalenes - pharmacology; Original Research; Particle Size; Patient satisfaction; PEG-PLGA; Permeability; Pharmaceutical sciences; Pharmacy; Polymers - chemistry; Premature ejaculation; Rats, Wistar; self-assembled core–shell nanostructures; Serotonin; Sexual disorders; Spectroscopy, Fourier Transform Infrared; Spectrum analysis; Saudi Arabia; United States > US; Egypt; brain delivery; nanotechnology; PEG–PLGA; self-assembled core–shell nanostructures; biodegradable copolymer
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S168148

Dapoxetine (DPX) is the drug of choice for the specific treatment of premature ejaculation. DPX is characterized by relatively low bioavailability (42%) and short half-life (1.5 h). The aim of this study was to improve DPX bioavailability and delivery across the blood-brain barrier (BBB) using a nanostructured DPX formulation for improved DPX efficacy and patient satisfaction. DPX-loaded polymeric micelles (PMs) formulations (F1-F3) were characterized for particle sizes, entrapment efficiencies, and Fourier transform infrared spectroscopic and transmission electron microscopic evaluations. In addition, diffusion profiles of the prepared formulations were investigated. Animal model pharmacokinetic parameters in plasma and brain tissues were investigated and compared with commercial DPX tablets. Particle size analysis revealed that formulations of DPX PMs showed a narrow range of 62.7±9.3-45.45±9.1 nm for F1-F3. In addition, DPX PMs showed a sustained release pattern with 91.27%±7.64%, 79.43%±7.81%, and 63.78%±5.05% of DPX content permeated after 24 h for F1, F2, and F3, respectively. Plasma pharmacokinetic parameters for DPX PMs showed significant increase ( <0.05) for the area under drug concentration-time curves in plasma and brain tissues compared with commercial DPX tablets. DPX formulations in the form of PMs improved bioavailability and efficacy across the BBB. This DPX formulation provided improved brain delivery in order to enhance the convenience and compliance of patients.