Modification of paclitaxel-loaded solid lipid nanoparticles with 2-hydroxypropyl-β-cyclodextrin enhances absorption and reduces nephrotoxicity associated with intravenous injection

Abstract

Jong-Suep Baek,* Ju-Heon Kim,* Jeong-Sook Park, Cheong-Weon Cho College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon, South Korea *These authors contributed equally to this work Background: Paclitaxel (PTX) solid lipid nanoparticles (SLNs) modified with 2-hydroxypropyl-β-cyclodextrin (HPCD) were evaluated for their ability to enhance PTX absorption and reduce the nephrotoxicity accompanying intravenous administration. Methods: PTX-loaded SLNs (PS) and PTX-loaded SLNs modified using HPCD (PSC) were prepared by hot-melted sonication. The anticancer activity of PSC was evaluated in MCF-7 cells, and confocal microscopy was used to quantify the cellular uptake. The pharmacokinetic profiles of PTX released from PSC after intravenous administration were studied in rats. Furthermore, kidney toxicity was determined by measuring the kidney size and plasma creatinine level. Results: PSC were successfully prepared by hot-melted sonication and had smaller diameters than PS. PSC exhibited improved anticancer activity and cellular uptake in MCF-7 cells. Furthermore, PSC showed higher bioavailability in rats after intravenous administration than PTX solution; however, no significant differences in kidney toxicity were observed. Conclusion: Based on these results, PSC could be considered as a potential therapeutic PTX delivery system for breast cancer with low renal toxicity. Keywords: paclitaxel, solid lipid nanoparticles, 2-hydroxypropyl-β-cyclodextrin, bioavailability, nephrotoxicity