title: Development of docetaxel-loaded solid self-nanoemulsifying drug delivery system (SNEDDS) for enhanced chemotherapeutic effect.
abstract: The main purpose of this study was to investigate the potential of self-nano-emulsifying drug delivery system (SNEDDS) in improving the bioavailability of docetaxel (DCT) and its chemotherapeutic effect. The DCT-loaded SNEDDS was prepared by employing rational blends of capryol 90, labrasol, and transcutol HP using ternary phase diagram. The liquid nano-emulsion was spray-dried into solid SNEDDS (D-SNEDDS) using an inert porous carrier, colloidal silica. The optimized formulation was characterized in terms of physico-chemical and pharmacokinetic parameters. Furthermore, anti-tumor efficacy of D-SNEDDS was compared with commercial marketed product, Taxotere(®). The various compositions of SNEDDS were screened and found optimal at a volume ratio of 10/75/15 for capryol 90, labrasol, and transcutol HP, respectively. We observed a high oral bioavailability of 17% DCT for D-SNEDDS than compared to only 2.6% for pure DCT solution. Notably, D-SNEDDS exhibited an augmented anti-tumor efficacy with a reduced toxicity profile when compared with intravenously administered Taxotere(®), the commercialized formulation of DCT. Taken together, D-SNEDDS could be a potential candidate for an oral dosage form of DCT with enhanced antitumor activity and reduced toxicity.
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.
authors.forename: Youn Gee
authors.initials: YG
authors.lastname: Seo
authors.forename: Dae Hwan
authors.initials: DH
authors.lastname: Kim
authors.forename: Thiruganesh
authors.initials: T
authors.lastname: Ramasamy
authors.forename: Jeong Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Nirmal
authors.initials: N
authors.lastname: Marasini
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
authors.forename: Dong-Wuk
authors.initials: DW
authors.lastname: Kim
authors.forename: Jin Ki
authors.initials: JK
authors.lastname: Kim
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D000077143:Docetaxel; D016503:Drug Delivery Systems; D004655:Emulsions; D005260:Female; D005989:Glycerides / Q000737:chemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D043823:Taxoids / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004655:Emulsions; D005989:Glycerides; D013501:Surface-Active Agents; D043823:Taxoids; D000077143:Docetaxel