Tamoxifen Citrate Loaded Solid Lipid Nanoparticles (SLN™): Preparation, Characterization, In Vitro Drug Release, and Pharmacokinetic Evaluation

Abstract

Solid lipid nanoparticles (SLN) were prepared by emulsification and high pressure homogenization technique and characterized by size analysis and differential scanning calorimetry. The influence of experimental factors such as homogenization pressure, time, and surfactant concentration on the nanoparticle size and distribution were investigated to optimize the formulation. Homogenization at 15,000 psi for 3 cycles was found to be optimum and resulted in smaller sized nanoparticles. In case of tristearin SLN (TSSLN), tripalmitin SLN (TPSLN), and glycerol behenate SLN (GBSLN), the relatively smaller sized nanoparticles were obtained with 3% sodium tauroglycocholate. The SLN were loaded with an anticancer agent, tamoxifen citrate (TC). The TC-loaded TSSLN shown lower entrapment efficiency (78.78%) compared to the TPSLN (86.75%) and GBSLN (98.64%). Short term stability studies indicated a significant increase in size of nanoparticles when stored at 50°C, compared to those stored at 30°C and 4°C. The particle destabilization upon storage in case of all the types of nanoparticles studied was in the order of day light > artificial light > dark. An ultraviolet (UV) spectrophotometric method of estimation of tamoxifen in rat plasma was developed and validated. The TC‐loaded TSSLN was administered to the rats intravenously and the pharmacokinetic parameters in the plasma were determined. The t_1/2 and mean residence time of TC-loaded TSSLN in plasma was about 3.5-fold (p < 0.001) and 3-fold (p < 0.001) higher, respectively, than the free tamoxifen, indicating the potential of TC-loaded TSSLN as a long circulating system in blood. Thus the above mentioned solid lipid nanoparticles can be a beneficial system to deliver tamoxifen to cancer tissues through enhanced permeability and retention (EPR) effect.

Keywords:

• solid lipid nanoparticles
• tamoxifen citrate
• pharmacokinetics
• drug delivery
• UV spectrophotometric method