RESEARCH ARTICLE Exploring solid lipid nanoparticles to enhance the oral bioavailability of curcumin Vandita Kakkar 1 , Sukhjit Singh 2 , Dinesh Singla 2 and Indu Pal Kaur 1 1 Department of Pharmaceutical Sciences, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India 2 Formulation Development, Panacea Biotec Ltd, Lalru, Punjab, India Received: July 8, 2010 Revised: August 16, 2010 Accepted: August 26, 2010 Scope: Curcumin, a molecule with pluripharmacological properties, was loaded into solid lipid nanoparticles (SLNs) with a view to improve its oral bioavailability (BA). Methods and results: Curcumin-loaded solid lipid nanoparticles (C-SLNs) with an average particle size of 134.6 nm and a total drug content of 92.3371.63% was produced using a microemulsification technique. The particles were spherical in shape, with high drug entrapment of 81.9272.91% at 10% drug loading. The in vitro release was predominantly by diffusion phenomenon and was prolonged up to 7 days. No significant variation in particle size and curcumin content of C-SLNs was observed, upon storage, over a period of 12 months at 5731C. In vivo pharmacokinetics performed after oral administration of C-SLNs (50, 25, 12.5 and 1 mg/kg dose) and (free) solubilized curcumin (C-S; 50 mg/kg), using a validated LC-MS/MS method in rat plasma revealed significant improvement (at po0.05) in BA (39 times at 50 mg/kg; 155 times at 1 mg/kg; and, 59 and 32 times at 12.5 and 25 mg/kg, respectively) after administration of C-SLNs at all the doses with respect to C-S. Conclusions: Enhanced and reliable BA will help in establishing its therapeutic usefulness especially for neurodegenerative and cancerous disorders in humans. Keywords: Bioavailability / Curcumin / LC-MS/MS / Liquid–liquid extraction / Solid lipid nanoparticles 1 Introduction Curcuma longa Linn. is one of several medicinal plants to have attracted the interest of scientists. For centuries it has acted as a remedy for several ailments, offering potential benefits in several chronic illnesses including neurodegenerative, anti- oxidant, cardiovascular, pulmonary, autoimmune and neoplastic diseases involving inflammation [1]. Despite multi- ple medicinal benefits, low oral bioavailability (BA) of curcu- min continues to be a major concern, irrespective of the route of administration. The latter is attributed to poor absorption, extensive intestinal and hepatic metabolism, rapid elimination and clearance from the body [2, 3]. Formulating curcumin for clinical efficacy has presented many challenges due to its poor physicochemical properties. In spite of the numerous formulation challenges, several strate- gies such as nanoparticles, liposomes, complexation with phospholipids and cyclodextrins and solid dispersions have been developed to improve the BA of curcumin [4–6]. Solid lipid nanoparticles (SLNs) loaded with curcuminoids for topi- cal application offered no significant improvement in comparison to that of the standard curcumin when tested in vitro (70% release in 12 h by SLN versus 90% release in 8 h by free curcumin) [6]. The synthesis of curcumin encapsulated polymeric nanoparticles of N-isopropylacrylamide, with N-vinyl-2-pyrrolidone and poly (ethyleneglycol) monoacrylate has been reported [4]. However, in vivo evaluation establishing the superiority of most of the above developed systems is still Abbreviations: BA, bioavailability; bw, body weight; C-S, solubilised curcumin; C-SLNs, curcumin-loaded solid lipid nanoparticles; IS, internal standard; SLN, solid lipid nanoparti- cles Correspondence: Dr. Indu Pal Kaur, University Institute of Phar- maceutical Sciences, Panjab University, Chandigarh 160014, India E-mail: indupalkaur@yahoo.com Fax: 191-172-2543101 & 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.mnf-journal.com Mol. Nutr. Food Res. 2011, 55, 495–503 495 DOI 10.1002/mnfr.201000310