title: Surface-modified solid lipid nanoparticles for oral delivery of docetaxel: enhanced intestinal absorption and lymphatic uptake.
abstract: Docetaxel is a potent anticancer drug, but development of an oral formulation has been hindered mainly due to its poor oral bioavailability. In this study, solid lipid nanoparticles (SLNs) surface-modified by Tween 80 or D-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS 1000) were prepared and evaluated in terms of their feasibility as oral delivery systems for docetaxel. Tween 80-emulsified and TPGS 1000-emulsified tristearin-based lipidic nanoparticles were prepared by a solvent-diffusion method, and their particle size distribution, zeta potential, drug loading, and particle morphology were characterized. An in vitro release study showed a sustained-release profile of docetaxel from the SLNs compared with an intravenous docetaxel formulation (Taxotere®). Tween 80-emulsified SLNs showed enhanced intestinal absorption, lymphatic uptake, and relative oral bioavailability of docetaxel compared with Taxotere in rats. These results may be attributable to the absorption-enhancing effects of the tristearin nanoparticle. Moreover, compared with Tween 80-emulsified SLNs, the intestinal absorption and relative oral bioavailability of docetaxel in rats were further improved in TPGS 1000-emulsified SLNs, probably due to better inhibition of drug efflux by TPGS 1000, along with intestinal lymphatic uptake. Taken together, it is worth noting that these surface-modified SLNs may serve as efficient oral delivery systems for docetaxel.
authors: College of Pharmacy, Kangwon National University, Chuncheon.
authors: Hyun-Jong
authors: HJ
authors: Cho
authors: College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam.
authors: Jin Woo
authors: JW
authors: Park
authors: College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam.
authors: In-Soo
authors: IS
authors: Yoon
authors: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Dae-Duk
authors: DD
authors: Kim
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077143:Docetaxel; D016503:Drug Delivery Systems; D007408:Intestinal Absorption; D008055:Lipids / Q000737:chemistry; D008208:Lymphatic System / Q000378:metabolism; D008297:Male; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols; D011136:Polysorbates; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014280:Triglycerides / Q000737:chemistry; D014810:Vitamin E / Q000031:analogs & derivatives
chemical_list: D000970:Antineoplastic Agents; D008055:Lipids; D011136:Polysorbates; D043823:Taxoids; D014280:Triglycerides; D014810:Vitamin E; D000077143:Docetaxel; D011092:Polyethylene Glycols; C014225:tocophersolan; C022618:tristearin
keywords: bioavailability; docetaxel; lymphatic uptake; solid lipid nanoparticles; toxicity; vitamin E TPGS