Exploring the physicochemical properties of the integration of Tristearoyl uridine in Langmuir monolayers: An approach to cell membrane modeling for prodrugs

Autor(es)

Moreira, Felipe Almeida ; Escobar, Jhon Fernando Berrio ; Giordani, Cristiano ; Caseli, Luciano

• Tipo de documento: Artigo Científico
• Fonte: Biophysical Chemistry; v. 310, p. 9-pg., 2024-05-09.

Resumo

Understanding the mechanisms by which drugs interact with cell membranes is crucial for unraveling the underlying biochemical and biophysical processes that occur on the surface of these membranes. Our research focused on studying the interaction between an ester-type derivative of tristearoyl uridine and model cell membranes composed of lipid monolayers at the air-water interface. For that, we selected a specific lipid to simulate nontumorigenic cell membranes, namely 1,2-dihexadecanoyl-sn-glycero-3-phospho-L-serine. We noted significant changes in the surface pressure-area isotherms, with a noticeable shift towards larger areas, which was lower than expected for ideal mixtures, indicating monolayer condensation. Furthermore, the viscoelastic properties of the interfacial film demonstrated an increase in both the elastic and viscous parameters for the mixed film. We also observed structural alterations using vibrational spectroscopy, which revealed an increase in the all-trans to gauche conformers ratio. This confirmed the stiffening effect of the prodrug on the lipid monolayer. In summary, this study indicates that this lipophilic prodrug significantly impacts the lipid monolayer's thermodynamic, rheological, electrical, and molecular characteristics. This information is crucial for understanding how the drug interacts with specific sites on the cellular membrane. It also has implications for drug delivery, as the drug's passage into the cytosol may involve traversing the lipid bilayer. (AU)

• Processo FAPESP: 23/00850-6 - Desenvolvimento de biossensores nanoestruturados para diagnóstico de biomarcadores de desordens mentais
• Beneficiário: Osvaldo Novais de Oliveira Junior
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 22/03736-7 - Estudos sobre a interação de compostos bioativos em modelos de biointerface e construção de dispositivos nanoestruturados bioinspirados
• Beneficiário: Luciano Caseli
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 22/13938-6 - Materiais nanoestruturados à base de nucleosídeos alquilados com propriedades anticancerígenos incorporados em filmes Langmuir e Langmuir-Blodgett de lipídeos e sondas luminescentes
• Beneficiário: Luciano Caseli
• Modalidade de apoio: Auxílio à Pesquisa - Regular