title: Optimization of process variables of zanamivir-loaded solid lipid nanoparticles and the prediction of their cellular transport in Caco-2 cell model.
abstract: The aim of this study was to optimize the process variables of zanamivir-loaded solid lipid nanoparticles (SLNs) and to predict their cellular transport across Caco-2 cell monolayers. Zanamivir-loaded SLNs were prepared by a double emulsion solvent evaporation method. The effects of process variables on the mean particle size and zeta potential of SLNs were investigated and the physicochemical properties of SLNs were characterized. In addition, the cytotoxicity and transport ability of SLNs were also studied in Caco-2 cell model. The mean particle size of drug-loaded SLNs was significantly affected by the process variables. The SLNs were prepared using glyceryl monosterate (1% polyvinyl alcohol (PVA) or 1.5% poloxamer 188 as surfactant) had a regular shape with a relatively lower mean particle size (324.2 and 224.9 nm, respectively), higher encapsulation efficacy (55.7 and 42.4%, respectively) and sustained drug release over 12h. The crystalline form of drug had been partly changed and no physicochemical interaction had occurred between drug and carriers in SLNs. The cell viability was approximately 100% even at a high concentration of blank SLNs. There was no remarkable difference in drug permeation between drug-loaded SLNs and drug solution at 2h, while drug-loaded SLNs showed a significant decrease in drug permeation compared with the drug solution at 4h. The process variables of zanamivir-loaded SLNs were successfully optimized in this study. However, these SLNs significantly reduced the transport ability of zanamivir across Caco-2 cell monolayers. Further studies are needed to fully understand the real absorption mechanism of developed SLNs.
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou Industrial Park, Suzhou, Jiangsu 215123, PR China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Shi
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou Industrial Park, Suzhou, Jiangsu 215123, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cao
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou Industrial Park, Suzhou, Jiangsu 215123, PR China.
authors.forename: Xiao-Yin
authors.initials: XY
authors.lastname: Zhu
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou Industrial Park, Suzhou, Jiangsu 215123, PR China.
authors.forename: Jing-Hao
authors.initials: JH
authors.lastname: Cui
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou Industrial Park, Suzhou, Jiangsu 215123, PR China. Electronic address: qrcao@suda.edu.cn.
authors.forename: Qing-Ri
authors.initials: QR
authors.lastname: Cao
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D001692:Biological Transport; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004075:Diglycerides / Q000737:chemistry; D065546:Drug Liberation; D005227:Fatty Acids / Q000737:chemistry; D005989:Glycerides / Q000737:chemistry; D006801:Humans; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D020442:Poloxamer / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013501:Surface-Active Agents / Q000737:chemistry; D014961:X-Ray Diffraction; D053243:Zanamivir / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D004075:Diglycerides; D005227:Fatty Acids; D005989:Glycerides; D013501:Surface-Active Agents; D020442:Poloxamer; C086409:glyceryl behenate; C048159:glyceryl monostearate; D011142:Polyvinyl Alcohol; C009032:precirol; D053243:Zanamivir
keywords: Caco-2 cell; Cellular transport; Process variables; Solid lipid nanoparticles; Zanamivir