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

• Main Authors: Abourehab MAS, Ahmed OAA, Balata GF, Almalki WH
• Format: Article
• Language: English
• Published: Dove Medical Press 2018-06-01
• Series: International Journal of Nanomedicine
• Subjects: PEG-PLGA; biodegradable copolymer; brain delivery; self-assembled core–shell nanostructures; nanotechnology
• Online Access: https://www.dovepress.com/self-assembled-biodegradable-polymeric-micelles-to-improve-dapoxetine--peer-reviewed-article-IJN

Mohammed AS Abourehab,1,2 Osama AA Ahmed,2,3 Gehan F Balata,4 Waleed H Almalki5 1Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Minia University, Minia, Egypt; 3Nanotechnology Laboratory, Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt; 5Department of Pharmacology and Toxicology, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia Background: 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. Materials and methods: 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. Results: 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 (P<0.05) for the area under drug concentration–time curves in plasma and brain tissues compared with commercial DPX tablets. Conclusion: 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. Keywords: PEG–PLGA, biodegradable copolymer, brain delivery, self-assembled core–shell nanostructures, nanotechnology