A Comprehensive Physicochemical Analysis Focusing on the Characterization and Stability of Valsartan Silver Nano-Conjugates

Valsartan (Val)-a lipophilic non-peptide angiotensin II type 1 receptor antagonist-is highly effective against hypertension and displaying limited solubility in water (3.08 μg/mL), thereby resulting in low oral bioavailability (23%). The limited water solubility of antihypertensive drugs can pose a challenge, particularly for rapid and precise administration. Herein, we synthesize and characterize valsartan-containing silver nanoparticles (Val-AgNPs) using <i>Mangifera indica</i> leaf extracts. The physicochemical, structural, thermal, and pharmacological properties of these nano-conjugates were established through various analytical and structural tools. The spectral shifts in both UV-visible and FTIR analyses indicate a successful interaction between the valsartan molecule and the silver nanoparticles. The resulting nano-conjugates are spherical and within the size range of 30-60 nm as revealed in scanning electron-EDS and atomic force micrographs. The log-normal distribution of valsartan-loaded nanoparticles, with a size range of 30 to 60 nm and a mode of 54 nm, indicates a narrow, monodisperse, and highly uniform particle size distribution. This is a favorable characteristic for drug delivery systems, as it leads to enhanced bioavailability and a consistent performance. Dynamic Light Scattering (DLS) analysis of the Val-AgNPs indicates a polydisperse sample with a tendency toward aggregation, resulting in larger effective sizes in the suspension compared to individual nanoparticles. The accompanying decrease in zeta potential (to -19.5 mV) and conductivity further supports the idea that the surface chemistry and stability of the nanoparticles changed after conjugation. Differential scanning calorimetry (DSC) demonstrated the melting onset of the valsartan component at 113.99 °C. The size-dependent densification of the silver nanoparticles at 286.24 °C correspond to a size range of 40-60 nm, showing a significant melting point depression compared to bulk silver due to nanoscale effects. The shift in Rf for pure valsartan to Val-AgNPs suggests that the interaction with the AgNPs alters the compound's overall polarity and/or its interaction with the stationary phase, complimented in HPTLC and HPLC analysis. The stability and offloading behavior of Val-AgNPs was observed at pH 6-10 and in 40% and 80% MeOH. In addition, Val-AgNPs did not reveal hemolysis or significant alterations in blood cell indices, confirming the safety of the nano-conjugates for biological application. In conclusion, these findings provide a comprehensive characterization of Val-AgNPs, highlighting their potential for improved drug delivery applications.