Green-synthesized silver-thalidomide nanoconjugates from Calotropis procera with enhanced anti-inflammatory via phospholipase A2 inhibition

The long clinical use of the potent anti-inflammatory and immunomodulatory drug thalidomide (TH) has been seriously limited by teratogenicity and dose-dependent toxicity. In this work, an environmentally friendly synthesis protocol of silver nanoparticles (AgNPs) utilizing the milky latex extract of Calotropis procera ( C. procera ) is presented. Later, these nanoparticles were conjugated with thalidomide to improve their compatibility and therapeutic performance. The formation of AgNPs was verified by a clear surface plasmon resonance band observed at 405 nm. Structural and chemical characterization through FTIR, Raman, XRD, SEM, and EDS analyses verified the crystalline metallic nature and phytochemical-mediated surface capping of the AgNPs, as well as successful conjugation of thalidomide on their surface. The resulting AgNPs-TH nanoconjugates (AT1-AT4) exhibited progressive spectral red shifts and morphological modifications, indicating increased drug loading. Anti-phospholipase A 2 (PLA 2 ) inhibition assays demonstrated concentration-dependent enhancement of anti-inflammatory activity, with AT4 achieving the highest inhibition of 74%, significantly higher than free thalidomide (42%). This improved activity was the result of a dual inhibition mechanism in which silver ions disrupted the Ca 2+ -dependent catalytic residues of PLA 2 , while thalidomide sterically blocked the hydrophobic substrate channel of the enzyme, thereby repressing the release of arachidonic acid. Thus, AgNPs-TH nanoconjugates synthesized through this green synthesis methodology could serve as a promising nanoplatform for anti-inflammatory applications, pending further biological safety evaluation.

Ҳали таржима қилинмаган