title: Dual approach utilizing self microemulsifying technique and novel P-gp inhibitor for effective delivery of taxanes.
abstract: In the present work, concomitant use of self-microemulsifying drug delivery systems (SMEDDS) and a novel third-generation P-gp inhibitor, GF120918 (elacridar), for the effective transport of taxanes (paclitaxel and docetaxel) across an in vitro model of the intestinal epithelium and uptake into tumor cells were investigated. On the basis of solubility studies and ternary phase diagrams, different SMEDDS formulations of taxanes were prepared and characterized. In caco-2 cell permeation study, paclitaxel-loaded SMEDDS along with GF120918 showed a four-fold increase in apparent permeability, while docetaxel-loaded SMEDDS in combination with GF120918 showed a nine-fold increase in permeability, as compared to plain drug solution. Cell uptake studies on A549 cells were performed with microemulsions formed from both SMEDDS formulations loaded with rhodamine 123 dye and showed good uptake than plain dye solution. Confocal laser scanning microscopic images further confirmed the higher uptake of both SMEDDS formulations in the presence of GF120918.
authors.affiliation: Faculty of Pharmacy, Hamdard University, New Delhi 110062, India. akashmph@gmail.com
authors.forename: Akash
authors.initials: A
authors.lastname: Chaurasiya
authors.forename: Ajeet K
authors.initials: AK
authors.lastname: Singh
authors.forename: Gaurav K
authors.initials: GK
authors.lastname: Jain
authors.forename: Musarrat H
authors.initials: MH
authors.lastname: Warsi
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Sublet
authors.forename: Farhan J
authors.initials: FJ
authors.lastname: Ahmad
authors.forename: Gerrit
authors.initials: G
authors.lastname: Borchard
authors.forename: Roop K
authors.initials: RK
authors.lastname: Khar
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000166:Acridines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D018938:Caco-2 Cells; D000077143:Docetaxel; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D017239:Paclitaxel / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D012995:Solubility; D043823:Taxoids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D044005:Tetrahydroisoquinolines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000166:Acridines; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D044005:Tetrahydroisoquinolines; D000077143:Docetaxel; C083501:Elacridar; D017239:Paclitaxel