title: Preparation and evaluation of charged solid lipid nanoparticles of tetrandrine for ocular drug delivery system: pharmacokinetics, cytotoxicity and cellular uptake studies.
abstract: In this study, tetrandrine-loaded cationic solid lipid nanoparticles (TET-CNP) and solid lipid nanoparticles (TET-NP) were prepared by the emulsion evaporation-solidification at low temperature method. The particle size, zeta potential, and entrapment efficiency of TET-CNP and TET-NP were characterized. The results showed that the TET-CNP and TET-NP had average diameters of (15.29 ± 1.34) nm and (18.77 ± 1.23) nm with zeta potentials of (5.11 ± 1.03) mV and (-8.71 ± -1.23) mV and entrapment efficiencies of (94.1 ± 2.37)% and (95.6 ± 2.43)%, respectively. In vitro release studies indicated that the TET-CNP and TET-NP retained the drug entity better than tetrandrine ophthalmic solutions (TET-SOL). In the pharmacokinetics studies, the AUC values of TET-CNP and TET-NP were 1.96-fold and 2.00-fold higher than that of TET-SOL ( p < 0.05); the Cmax values of TET-CNP and TET-NP were 2.45-fold and 2.53-fold higher than that of the TET-SOL (p < 0.05), respectively. Cytotoxicity study showed that TET-CNP and TET-NP had no significant toxicity at low concentrations. Flow cytometry studies and confocal microscopy analysis demonstrated that calcein labeled NP (CA-NP) uptake by SRA 01/04 cells was much higher than those of calcein labeled CNP (CA-CNP) and calcein solution (CA-SOL).
authors.affiliation: Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education , Tianjin 300193 , P.R. China .
authors.forename: Jiawei
authors.initials: J
authors.lastname: Li
authors.forename: Xiujun
authors.initials: X
authors.lastname: Guo
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Liu
authors.forename: Chukwunweike Ikechukwu
authors.initials: CI
authors.lastname: Okeke
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Hainan
authors.initials: H
authors.lastname: Zhao
authors.forename: Mike Okweesi
authors.initials: MO
authors.lastname: Aggrey
authors.forename: Weisan
authors.initials: W
authors.lastname: Pan
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D044182:Benzylisoquinolines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D002152:Calorimetry, Differential Scanning; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D004847:Epithelial Cells / Q000187:drug effects; D005123:Eye / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D017551:Microdialysis; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D009883:Ophthalmic Solutions; D010316:Particle Size; D011817:Rabbits; D013499:Surface Properties
chemical_list: D044182:Benzylisoquinolines; D004337:Drug Carriers; D008055:Lipids; D009883:Ophthalmic Solutions; C009438:tetrandrine
keywords: Cellular uptake; cytotoxicity; ocular solid lipid nanoparticles; pharmacokinetics; tetrandrine