Effects of Formulation Variables on the Particle Size and Drug Encapsulation of Imatinib-Loaded Solid Lipid Nanoparticles

Abstract

Imatinib (IMT), an anticancer agent, inhibits receptor tyrosine kinases and is characterized by poor aqueous solubility, extensive first-pass metabolism, and rapid clearance. The aims of the current study are to prepare imatinib-loaded solid lipid nanoparticles (IMT-SLN) and study the effects of associated formulation variables on particle size and drug encapsulation on IMT-SLN using an experimental design. IMT-SLN was optimized by use of a "combo" approach involving Plackett-Burman design (PBD) and Box-Behnken design (BBD). PBD screening resulted in the determination of organic-to-aqueous phase ratio (O/A), drug-to-lipid ratio (D/L), and amount of Tween(R) 20 (Tw20) as three significant variables for particle size (S-z), drug loading (DL), and encapsulation efficiency (EE) of IMTSLN, which were used for optimization by BBD, yielding an optimized criteria of O/A=0.04, D/L=0.03, and Tw20=2.50%w/v. The optimized IMT-SLN exhibited monodispersed particles with a size range of 69.0 +/- 0.9 nm, zeta-potential of -24.2 +/- 1.2 mV, and DL and EE of 2.9 +/- 0.1 and 97.6 +/- 0.1% w/w, respectively. Results of in vitro release study showed a sustained release pattern, presumably by diffusion and erosion, with a higher release rate at pH 5.0, compared to pH 7.4. In conclusion, use of the combo experimental design approach enabled clear understanding of the effects of various formulation variables on IMT-SLN and aided in the preparation of a system which exhibited desirable physicochemical and release characteristics.