Sustained Release and Enhanced Bioactivity of Thymol Loaded Gold-Silver Bimetallic Nanocomplex: Synthesis, Characterization and Therapeutic Evaluation
摘要
Thymol, a bioactive monoterpenoid, possesses manifold pharmacological properties but limited clinical applicability due to low aqueous solubility and bioavailability. To overcome these constraints, thymol-loaded metal nanoformulations were fabricated, including thymol-loaded gold nanoparticles (T@AuNPs), thymol-loaded silver nanoparticles (T@AgNPs), and thymol-loaded gold–silver bimetallic nanocomplexes (T@AuAg). The bimetallic nanoformulation was optimized using Design Expert software to obtain minimal particle size and maximal encapsulation efficiency, yielding an optimal composition of 1.0% gold and 8.01% silver with a particle size of 102 nm (by dynamic light scattering), zeta potential of -27.4 mV and 89% encapsulation efficiency indicating good colloidal stability. Structural and morphological analysis by Transmission Electron Microscopy confirmed uniform spherical T@AuAg nanocomplexes with a size ranging from 60 to 70 nm. In vitro studies compared monometallic and bimetallic nanoformulations with pure thymol across drug release, antimicrobial, antioxidant, hemolysis assay, and antidiabetic assays. Pure thymol showed rapid release (95 ± 0.2% in 6 h), whereas T@AuAg exhibited sustained release (96 ± 0.2% over 24 h), with T@AgNPs and T@AuNPs also demonstrating prolonged release profiles. The bimetallic nanocomplex displayed stronger antibacterial activity against multiple bacterial strains than pure thymol and monometallic formulations. Antioxidant activity of T@AuAg nanocomplex (96.3 ± 0.2%) exceeded that of monometallic nanoparticles and free thymol, and anti-inflammatory (97.2 ± 0.25%) and antidiabetic (84.2 ± 0.2%) activities were similarly enhanced compared to controls and monometallic nanoformulations. Overall, thymol loaded bimetallic nanocomplexes improved stability, sustained release, and biological efficacy, establish T@AuAg bimetallic nanocomplex as a promising nanocarrier system for thymol-based drug delivery.
Graphical Abstract