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Development of albumin nanoparticles as a vehicle of seriniquinone

Grant number: 20/09270-4
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2020
Effective date (End): August 31, 2022
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal researcher:Leticia Veras Costa Lotufo
Grantee:Rodrigo dos Anjos Miguel
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:15/17177-6 - Integrative approach on the sustainable prospection of marine natural products: from diversity to anticancer compounds, AP.BTA.TEM

Abstract

Melanoma is one of the most aggressive cancers with increasing incidence, therapies that confer resistance and various adverse effects. Novel drugs with different therapeutic targets and mechanisms of action consist in an attempt to overcome these barriers. In this context, seriniquinone (SQ), synthesized by a rare Gram-positive marine bacterium from the genus Serinicoccus, was described as a high selective and cytotoxic agent to melanoma cell lines. However, SQ is poor soluble in water (0,06µM), what makes unfeasible its formulation and therapeutic use. Thereby, this project aims the development and the evaluation of albumin nanoparticles for SQ encapsulation. These nanocarriers confer stability, biodegradability, non-toxicity, non-immunogenicity, different sites for binding/interaction with molecules of interest and increasing in apparent solubility of hydrophobic drugs. Additionally, albumin nanoparticles also allow passive and active targeting (by surface modification), which is interesting for the non-selective toxicity of anticancer drugs and a highly metastatic disease with fenestrated and permeable vessels. Different techniques will be studied to develop the formulations: desolation, crosslinking, high pressure homogenization and sonication. Besides, the charge, size distribution, encapsulation efficiency and morphology of these nanoparticles will be characterized by dynamic light scattering (DLS), transmission and scanning electronic microscopy. Also, the cytotoxicity of these nanoparticles will be evaluated in melanoma cells using 2D and 3D systems.

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