title: Design, characterization, and in vitro cellular inhibition and uptake of optimized genistein-loaded NLC for the prevention of posterior capsular opacification using response surface methodology.
abstract: This study was to design an innovative nanostructured lipid carrier (NLC) for drug delivery of genistein applied after cataract surgery for the prevention of posterior capsular opacification. NLC loaded with genistein (GEN-NLC) was produced with Compritol 888 ATO, Gelucire 44/14 and Miglyol 812N, stabilized by Solutol(®) HS15 by melt emulsification method. A 2(4) central composite design of 4 independent variables was performed for optimization. Effects of drug concentration, Gelucire 44/14 concentration in total solid lipid, liquid lipid concentration, and surfactant concentration on the mean particle size, polydispersity index, zeta potential and encapsulation efficiency were investigated. Analysis of variance (ANOVA) statistical test was used to assess the optimization. The optimized GEN-NLC showed a homogeneous particle size of 90.16 nm (with PI=0.33) of negatively charged surface (-25.08 mv) and high encapsulation efficiency (91.14%). Particle morphology assessed by TEM revealed a spherical shape. DSC analyses confirmed that GEN was mostly entrapped in amorphous state. In vitro release experiments indicated a prolonged and controlled genistein release for 72 h. In vitro growth inhibition assay showed an effective growth inhibition of GEN-NLCs on human lens epithelial cells (HLECs). Preliminary cellular uptake test proved a enhanced penetration of genistein into HLECs when delivered in NLC.
authors.affiliation: School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Wenji
authors.initials: W
authors.lastname: Zhang
authors.forename: Xuedong
authors.initials: X
authors.lastname: Li
authors.forename: Tiantian
authors.initials: T
authors.lastname: Ye
authors.forename: Fen
authors.initials: F
authors.lastname: Chen
authors.forename: Xiao
authors.initials: X
authors.lastname: Sun
authors.forename: Jun
authors.initials: J
authors.lastname: Kong
authors.forename: Xinggang
authors.initials: X
authors.lastname: Yang
authors.forename: Weisan
authors.initials: W
authors.lastname: Pan
authors.forename: Sanming
authors.initials: S
authors.lastname: Li
mesh_terms: D000704:Analysis of Variance; D058442:Capsule Opacification / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002460:Cell Line; D002463:Cell Membrane Permeability; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005227:Fatty Acids / Q000737:chemistry; D019833:Genistein / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D015233:Models, Statistical; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D057852:Posterior Capsule of the Lens / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors; D014280:Triglycerides / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D005227:Fatty Acids; D008055:Lipids; D013229:Stearic Acids; D013501:Surface-Active Agents; D014280:Triglycerides; C104509:gelucire 44-14; C086409:glyceryl behenate; C022834:miglyol 812; D011092:Polyethylene Glycols; C067028:Solutol HS 15; D019833:Genistein
keywords: Cellular uptake; Central composite design; Genistein; Inhibition; Nanostructured lipid carrier; Posterior capsular opacification