title: Optimization of controlled release nanoparticle formulation of verapamil hydrochloride using artificial neural networks with genetic algorithm and response surface methodology.
abstract: This study was performed to optimize the formulation of polymer-lipid hybrid nanoparticles (PLN) for the delivery of an ionic water-soluble drug, verapamil hydrochloride (VRP) and to investigate the roles of formulation factors. Modeling and optimization were conducted based on a spherical central composite design. Three formulation factors, i.e., weight ratio of drug to lipid (X1), and concentrations of Tween 80 (X2) and Pluronic F68 (X3), were chosen as independent variables. Drug loading efficiency (Y1) and mean particle size (Y2) of PLN were selected as dependent variables. The predictive performance of artificial neural networks (ANN) and the response surface methodology (RSM) were compared. As ANN was found to exhibit better recognition and generalization capability over RSM, multi-objective optimization of PLN was then conducted based upon the validated ANN models and continuous genetic algorithms (GA). The optimal PLN possess a high drug loading efficiency (92.4%, w/w) and a small mean particle size (∼100nm). The predicted response variables matched well with the observed results. The three formulation factors exhibited different effects on the properties of PLN. ANN in coordination with continuous GA represent an effective and efficient approach to optimize the PLN formulation of VRP with desired properties.
authors.affiliation: Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada; Targeted Drug Delivery Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohammadreza R
authors.initials: MR
authors.lastname: Abbaspour
authors.affiliation: Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada; Department of Economics, McMaster University, Hamilton, ON L8S 4M4, Canada.
authors.forename: Paul V
authors.initials: PV
authors.lastname: Grootendorst
authors.affiliation: Faculty of Medicine, University of Toronto, ON M5G 2M9, Canada.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Rauth
authors.affiliation: Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada. Electronic address: xywu@phm.utoronto.ca.
authors.forename: Xiao Yu
authors.initials: XY
authors.lastname: Wu
mesh_terms: D000465:Algorithms; D002121:Calcium Channel Blockers / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003198:Computer Simulation; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D008956:Models, Chemical; D050997:Nanomedicine; D053758:Nanoparticles; D016571:Neural Networks, Computer; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011136:Polysorbates / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*; D014700:Verapamil / Q000737:chemistry*
chemical_list: D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008055:Lipids; D011108:Polymers; D011136:Polysorbates; D020442:Poloxamer; D014700:Verapamil
keywords: Artificial neural networks; Continuous genetic algorithm; Optimization; Polymer–lipid hybrid nanoparticles; Response surface methodology; Verapamil hydrochloride