PEGylated solid lipid nanoparticles: design, methotrexate loading and biological evaluation in animal models

Abstract

The poor bioavailability of chemotherapeutic drugs, such as methotrexate (MTX), plays a critical role in their success. Solid lipid nanoparticles (SLNs) have emerged as vital therapeutic carriers owing to the biocompatible nature of their constituent materials. In this study, a nanoparticulate system, consisting of a pegylated lipid core of stearic acid, has been designed to evaluate its potential for encapsulation and delivery of the chemotherapeutic drug MTX, which often suffers from poor bioavailability. Stable pegylated SLN formulations of MTX having a mean particle size ~130 nm (zeta potential −34 mV) and low polydispersity were prepared and completely characterized using DSC, TEM and AFM. They were found to present an almost spherical morphology. These drug-loaded formulations were found to have good hemocompatibility, as quantified by hemolysis analysis. In vitro drug release studies at acidic pH (5.5) and physiological pH (7.4) revealed a power-law mechanism of release of MTX from the SLNs. These MTX-loaded formulations have been evaluated biologically with the help of radiolabeling techniques (with ^99mTc radionuclide). The blood kinetics profile of the ^99mTc radiolabeled pegylated MTX formulations in New Zealand Albino rabbits revealed higher blood circulation times, while the biodistribution studies in tumour models (balb/c mice) revealed their efficient tumour uptake, as evidenced by SPECT imaging. These studies convey the potential use of these pegylated SLNs based on stearic acid for improving the bioavailability of MTX and they can be expected to be a valuable addition to the array of nanoparticles with potential therapeutic applications.