Development and characterization of polycaprolactone nanoparticles containing paclitaxel: a potential delivery system for the treatment of ovarian cancer

Abstract

Cancer is currently considered one of the most lethal diseases; it happens because of malfunction of genes that control cell growth and division, being the second most deadly disease in the United States with 580,000 deaths estimated in 2013. Ovarian cancer (adenocarcinoma) is the fourth cause of death from cancer. And for being the most lethal gynecologic tumors, was responsible for 3,027 deaths in 2011 in Brazil, and 5,680 new cases are estimated in 2014. Due to its location, ovarian cancer has a very difficult detection, and is considered the least curable by already being evolved at the time of diagnosis. The treatment of this cancer includes cycles of chemotherapy and surgery followed by chemotherapy sessions. However, the benefits of chemotherapy are limited due to toxicity of chemotherapeutic drugs on normal tissues. The paclitaxel is the drug used as first and second treatment line of ovarian carcinoma, but because of its low solubility in water, this drug has a reduced bioavailability. Due to this limitation, the commercial drug (Taxol®) is formulated with a solution containing Cremophor® EL and ethanol. Meantime, this solution has a high toxicity, which generates several adverse effects. Furthermore, the process of drug resistance happens frequently, but has not yet been fully studied. Nanotechnology has become a very promising and utilized technology in pharmaceutical area, through the development of nanocarriers, such as polymeric nanoparticles. These nanocarriers have functions like drug protection against degradation, increasing bioavailability, toxicity reduction, increasing the amount of drug released on the tumor, improve the chemotherapeutic drugs solubility. Therefore, the objective of this work is to develop and characterize polymeric nanoparticles containing paclitaxel, aiming the optimization of the ovarian cancer's treatment. The physico-chemical characterization will include analysis and distribution of nanoparticle size by light scattering, zeta potential analysis, evaluation of efficiency of paclitaxel's encapsulation by HPLC, differential scanning calorimetry, Fourier transform infrared spectroscopy (FTIR). And then, will be made the assessment of the study of in vitro release profile of paclitaxel comparing the profile of commercial paclitaxel (Taxol®) with the obtained system. The results obtained with this proposal will be used in another research project that will evaluate the effectiveness of this delivery system in the treatment of ovarian cancer models in vitro and in vivo.