Docetaxel loaded-immunoliposomes: in vitro effect in 3D multicellular tumor spheroids of prostate cancer cell culture

• Grant number: 18/21104-2
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Effective date (Start): January 15, 2019
• Effective date (End): May 14, 2019
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Marlus Chorilli
• Grantee: Felipe Tita de Lima
• Supervisor: Wafa Al-Jamal
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Research place: Queen's University Belfast, Northern Ireland
• Associated to the scholarship: 18/00814-1 - Development and characterization of lyophilized liposomes and immunoliposomes containing docetaxel for potential application in the prostate cancer treatment, BP.IC

Abstract

Prostate cancer is the second most common type of cancer worldwide, which indicates a serious public health problem. Docetaxel is one of the main chemotherapeutic agents for the treatment, even though some of its physicochemical properties limit its therapeutic use, such as low solubility in water and toxicity. Encapsulation in nanocarriers, especially liposomes, has the potential to improve docetaxel's properties. However, as liposomal formulations may face physico-chemical instability in aqueous dispersions, it is necessary to employ methods to prolong liposome stability, the freeze-drying being the most common of those methods. The functionalization of liposomes with monoclonal antibodies has the potential to increase the selectivity and efficacy of the treatment. Thus, cetuximab is a monoclonal antibody potentially applicable for prostate cancer treatment, since cancer cells can overexpress the EGFR (Epidermal Growth Factor Receptor), which binds to cetuximab. Therefore, the strategy of functionalized liposomes with cetuximab is potentially advantageous. Thus, this study will consist of characterization and in vitro evaluation of cetuximab conjugated liposomes, prepared by the classic thin lipid film method and extrusion, containing encapsulated docetaxel, in 3D multicellular tumor spheroids (MTS) of a prostate cancer cell culture (DU145). The efficacy of the formulations will be investigated by cell cytotoxicity and the uptake cellular will be evaluated by confocal microscopy and flow cytometry. (AU)