title: Nanoparticulate formulations for paclitaxel delivery across MDCK cell monolayer.
abstract: Paclitaxel appears to be a potential substrate of the multidrug resistance protein p-glycoprotein, thus preventing itself from entry into the brain and penetrating blood-brain barrier poorly. In this study, the main objective was to design paclitaxel formulation using PLGA-based nanoparticles with different additives and surface coatings to facilitate the paclitaxel transport through MDCK cell monolayer. PLGA-based nanoparticles of around 200 nm without and with additives and surface coatings were developed by direct dialysis. The transendothelial electrical resistance (TEER) variation of MDCK cell monolayer on the cell inserts imposed by paclitaxel-loaded nanoparticles with and without additives was investigated. (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole) (MTT) assay was used to quantify the cell viability of C6 glioma cells after administration of formulations on the topical side. Investigations showed that particles with additives were able to enhance cellular uptake more than surface-coated particles. TEER values dropped upon the introduction of paclitaxel-loaded PLGA nanoparticles to the cell inserts. After incubation for 24 h, the cell viability of C6 glioma cells in the wells treated with nanoparticles was lower than that of the control wells without particles. Taken together, PLGA nanoparticles with vitamin E TPGS and polysorbate 80 as additives were successfully obtained as paclitaxel formulations, demonstrating great potential for the delivery of paclitaxel through MDCK cell monolayer in vitro.
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering, Drive 4, 117576, Singapore.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Xie
authors.forename: Chenlu
authors.initials: C
authors.lastname: Lei
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
authors.forename: Gary Kaizhong
authors.initials: GK
authors.lastname: Gay
authors.forename: Nazrul Hadi
authors.initials: NH
authors.lastname: Bin Jamali
authors.forename: Chi-Hwa
authors.initials: CH
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods*; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017239:Paclitaxel