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Development and characterization of lyophilized liposomes and immunoliposomes containing docetaxel for potential application in the prostate cancer treatment

Grant number: 18/00814-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2018
Effective date (End): September 30, 2019
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Marlus Chorilli
Grantee:Felipe Tita de Lima
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated scholarship(s):18/21104-2 - Docetaxel loaded-immunoliposomes: in vitro effect in 3D multicellular tumor spheroids of prostate cancer cell culture, BE.EP.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 treatment, even though some of its characteristics 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 receptor (Epidermal Growth Factor Receptor), which binds to cetuximab. Therefore, the strategy of functionalization liposomes with cetuximab is potentially advantageous. Therefore, this project aims to develop and characterize lyophilized liposomes and immunoliposomes, functionalized with cetuximab, containing docetaxel for potential application in the prostate cancer treatment. It is contemplated the characterization of the systems by particle size, polydispersity, zeta potential, encapsulation efficiency of docetaxel, infrared spectroscopy, differential scanning calorimetry, and in vitro release of docetaxel. Additionally, the conjugation efficiency of the antibody to the liposomes will be evaluated by the bicinchonin acid assay and the integrity of the antibody will be investigated by electrophoresis and circular dichroism.

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