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

Author(s)

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

• Document type: Journal article
• Source: Biophysical Chemistry; v. 310, p. 9-pg., 2024-05-09.

Abstract

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)

• FAPESP's process: 23/00850-6 - Development of nanostructured biosensors for the diagnosis of mental disorders biomarkers
• Grantee: Osvaldo Novais de Oliveira Junior
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/03736-7 - Nanostructured interfaces for the investigation of bioactive substances in cell membrane models and for the construction of optoelectronic devices
• Grantee: Luciano Caseli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/13938-6 - Nanostructured materials based on alkylated nucleosides with anticancer properties incorporated in Langmuir and Langmuir-Blodgett films of lipids and luminescent probes
• Grantee: Luciano Caseli
• Support Opportunities: Regular Research Grants