abstract

Recently, nanoparticle-based drug delivery systems have been proposed as new methods to enhance the therapeutic efficacy, bioavailability, and safety of drugs while reducing their toxic side effects. The current study attempted to develop, optimize, and evaluate the anti-tumor activity of a nanoparticle-based formulation of a drug using a polymer-based delivery system for better therapeutic performance. The drug loaded nanoparticles were synthesized and optimized through a Box–Behnken experimental design in order to provide desirable physicochemical properties such as particle size, polydispersity index, zeta potential, drug loading and entrapment efficiency. Characterization of the optimized nanoparticle formulation was performed through scanning electron microscopy, transmission electron microscopy, FTIR spectroscopy, differential scanning calorimetry, X-ray diffraction and drug release study in vitro. The biological activity of the optimized formulation was investigated using MTT cytotoxicity assay, live/dead assay, cellular uptake, intracellular reactive oxygen species production, apoptosis and hemocompatibility test. Anticancer efficacy in vivo was evaluated in an experimentally induced tumor bearing rat model based on the tumor volume, tumor inhibition, body weight, survival rate, activity of the antioxidant enzymes and changes in histopathology. The optimized drug loaded nanoparticles possessed excellent physicochemical characteristics, drug release pattern, high cellular uptake and more cytotoxic effect than the pure drug. The results obtained from in vivo study showed a significant inhibition of tumor growth, increase in body weight, increase in survival rate, recovery of superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione content in addition to decreased level of malondialdehyde. The histopathology of the treated tissues revealed preservation of normal tissue architecture and reduced pathological changes due to nanoparticle treatment. Generally, the optimized nanoparticle formulation exhibited higher antitumor and antioxidant activity and better biocompatibility than the drug formulation.