Spectroscopic and Computational Insights into the Effects of Physicochemical Parameters on Antimalarial Drug-Albumin Interactions: A Comprehensive Review

Serum albumin is a key factor in the transport, bioavailability, and overall pharmacokinetics of many therapeutic agents. For antimalarial drugs such as sulfadoxine and pyrimethamine, it is crucial to study how albumin affects them under different physicochemical conditions to predict and determine drug distribution, resistance development, and efficacy. The review is a synthesis of the results reported in the literature on fluorescence spectroscopy, UV-Vis absorption, FTIR, circular dichroism, and molecular docking research that characterize drug-albumin interaction. The focus is on the effects of temperature, pH, and ionic strength on binding affinity, quenching mechanisms, structural perturbation, and interactions with protein residues. In most studies, some drugs consistently bind to Sudlow site I (subdomain IIA), while others bind to site II (subdomain IIIA), and binding mostly causes stationary quenching of the albumin structure with slight conformational changes. Temperature-dependent decreases in binding affinity confirm exothermic complexation, whereas drug ionization is influenced by pH and electrostatic complementarity by ionic strength. Docking experiments complement the spectroscopic results by showing that hydrogen bonding and hydrophobic interactions are key stabilizing forces. The review highlights discrepancies across studies due to methodological differences and the need for standardized experimental conditions and complementary computational validation. This synthesis provides a mechanistic basis for predicting drug-protein interactions under physiologically relevant conditions and highlights gaps that future studies need to address.