Surface-modified solid lipid nanoparticles for oral delivery of docetaxel: enhanced intestinal absorption and lymphatic uptake

• Published in: International journal of nanomedicine Vol. 9; no. Issue 1; pp. 495 - 504
• Main Authors: Cho, Hyun-Jong, Park, Jin Woo, Yoon, In-Soo, Kim, Dae-Duk
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01-01-2014; Dove Press; Dove Medical Press
• Subjects: Administration, Oral; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; bioavailability; Complications and side effects; Docetaxel; Dosage and administration; Drug Delivery Systems; Drugs; Intestinal Absorption; Lipids - chemistry; Lymphatic System - metabolism; lymphatic uptake; Male; Nanomedicine; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Original Research; Polyethylene Glycols; Polysorbates; Properties; Rats; Rats, Sprague-Dawley; solid lipid nanoparticles; Surface Properties; Taxoids - administration & dosage; Taxoids - pharmacokinetics; toxicity; Triglycerides - chemistry; Vehicles; Vitamin E - analogs & derivatives; vitamin E TPGS; South Korea; toxicity; lymphatic uptake; bioavailability; docetaxel; vitamin E TPGS; solid lipid nanoparticles
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S56648

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.