Brazilian Red Propolis Extract-Loaded Colloidal Systems Derived from Microemulsion Compositions: Physicochemical,...

Background/Objectives: Brazilian red propolis is a rich source of isoflavonoids with promising antioxidant and antileishmanial activities. However, its poor aqueous solubility and chemical instability limit its pharmaceutical application. This study aimed to develop microemulsion-based systems containing high concentrations of Brazilian red propolis extract (RPE) and evaluate their physicochemical properties, phytochemical composition, antioxidant capacity, and antileishmanial activity. Methods: Pseudoternary phase diagrams were constructed by water titration to select suitable microemulsion compositions. RPE was subsequently incorporated into the selected compositions to obtain RPE-loaded colloidal systems. The three selected RPE-free microemulsions and their corresponding RPE-loaded systems were characterized by pH, electrical conductivity, dynamic light scattering, rheological measurements, and polarized light microscopy (PLM). The RPE-loaded systems were further evaluated for phenolic marker content, antioxidant activity, and in vitro activity against Leishmania infantum. Results: Three RPE-loaded colloidal systems (F2-RPE12, F3-RPE30, and F4-RPE50) were developed. F2-RPE12 exhibited characteristics consistent with an oil-in-water microemulsion. Conductivity and PLM indicated physicochemical changes after RPE incorporation in F3-RPE30 and F4-RPE50, with localized birefringent features at higher RPE concentrations. Among the RPE-loaded systems, F4-RPE50 showed the highest phenolic and flavonoid contents and antioxidant activity. The RPE-loaded systems exhibited lower IC₅₀ values than RPE alone, with IC₅₀ values of 3.14, 2.28, and 0.56 µg·mL^-1 for F2-RPE12, F3-RPE30, and F4-RPE50, respectively, compared with 5.90 µg·mL^-1 for RPE. Conclusions: Overall, F4-RPE50 showed the most favorable phytochemical and biological performance, and the physicochemical and optical changes observed in the RPE-loaded systems open new avenues for investigating the relationship between structural organization and formulation performance.