Breast cancer represents an important problem in public health, being one of the leading causes of death among women. The treatment of the pathology varies depending on the biochemical characteristics of the tumor. Among the drugs used in the therapy, one of the most employed is paclitaxel, a cytotoxic agent with high potency and efficacy; however, it is associated with several side effects, because of drug and also due to the formulation composition. Hydrocloride metformin, traditionally used to treat diabetes, has been reported as a promising drug for cancer treatment, although the drug is very hydrophilic. Another drug that should be highlighted is rapamycin, commonly used as a immunosuppressant, which has been shown to have potent anticancer activity, particularly against breast cancer. However, it is a lipophilic drug, undergoes erythrocytes sequestration and is chemically unstable, factors that compromise bioavailability. The association between paclitaxel with metformin or rapamycin could be useful to treat breast cancer. Cases of breast cancer with overexpression of HER2 receptor are also very aggressive and therapy with the antibody anti-HER2 has been used successfully. Still, this antibody, trastuzumab (Herceptin®), could be used in pharmaceutical technology to target delivery systems to the cancer cells, enabling site-specific drug release. Based on this, the purpose of the present project is to develop and characterize long-circulating liposomes, carrying paclitaxel, metformin and/or rapamycin. The developed system will be targeted with trastuzumab. Physical chemical characterization will involve the determination of encapsulation efficiency, evaluation of antibody integrity, particle size measurement, zeta potential determination, morphology determination using transmission electronic microscopy, analysis of FTIR, DSC, TGA and in vitro drug release profile. Cellular uptake and localization of the liposomes will be evaluated using confocal microscopy and flow cytometry. Finally, liposomes and immunoliposomes will be evaluated for breast cancer efficacy in vitro, in cells, and in vivo, in an animal model.
News published in Agência FAPESP Newsletter about the scholarship: