title: Optimization of long circulating mixed polymeric micelles containing vinpocetine using simple lattice mixture design, in vitro and in vivo characterization.
abstract: The aim of this study was to increase the in vivo mean residence time of vinpocetine after IV injection utilizing long circulating mixed micellar systems. Mixed micelles were prepared using Pluronics L121, P123 and F127. The systems were characterized by testing their entrapment efficiency, particle size, polydispersity index, zeta potential, transmission electron microscopy and in vitro drug release. Simple lattice mixture design was planned for the optimization using Design-Expert(®) software. The optimized formula was lyophilized, sterilized and imaged by scanning electron microscope. Moreover, the in vivo behavior of the optimized formula was evaluated after IV injection in rabbits. The optimized formula, containing 68% w/w Pluronic L121 and 32% w/w Pluronic F127, had the highest desirability value (0.621). Entrapment efficiency, particle size, polydispersity index and zeta potential of the optimized formula were 50.74 ± 3.26%, 161.50 ± 7.39 nm, 0.21 ± 0.03 and -22.42 ± 1.72 mV, respectively. Lyophilization and sterilization did not affect the characteristics of the optimized formula. Upon in vivo investigation in rabbits, the optimized formula showed a significantly higher elimination half-life and mean residence time than the market product. Finally, mixed micelles could be considered as a promising long circulating nanocarrier for lipophilic drugs.
authors.affiliation: Pharmaceutics Department, Faculty of Pharmacy, October 6 University, Egypt.
authors.forename: Rania Moataz
authors.initials: RM
authors.lastname: El-Dahmy
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; College of Pharmacy, Gulf Medical University, Ajman, United Arab Emirates. Electronic address: ibrahim.elsayed@pharma.cu.edu.eg.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Elsayed
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; School of Pharmacy, University of Waterloo, ON, Canada.
authors.forename: Ahmed Hassen
authors.initials: AH
authors.lastname: Elshafeey
authors.affiliation: Pharmaceutics Department, Faculty of Pharmacy, October 6 University, Egypt.
authors.forename: Nabaweya Abdelaziz Abd El
authors.initials: NA
authors.lastname: Gawad
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Omaima Naim
authors.initials: ON
authors.lastname: El-Gazayerly
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005612:Freeze Drying; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D008823:Micelles; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D011817:Rabbits; D014748:Vinca Alkaloids / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000959:Antihypertensive Agents; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D014748:Vinca Alkaloids; C013983:vinpocetine
keywords: Lyophilization; Mannitol (PubChem CID: 6251); Mean residence time; Micelles; Pluronic; Pluronics (PubChem CID: 24751); Sodium lauryl sulphate (PubChem CID: 3423265); Sterilization; Vinpocetine; Vinpocetine (PubChem CID: 443955); Vivo