Development of Carvacrol-Loaded Albumin Nanoparticles: Evaluation of Antimicrobial Activity Against Aquaculture Pathogens and Controlled Release Propertiese Pathogens

The increasing prevalence of bacterial infections in aquaculture highlights the growing need forenvironmentally friendly and effective antimicrobial strategies. This study aimed to develop and evaluateCarvacrol-loaded human serum albumin nanoparticles (CRV-Al@NPs) as a controlled-release system withantibacterial activity against aquaculture pathogens. CRV-Al@NPs were successfully prepared using amodified desolvation method, achieving high encapsulation efficiency (81.7±2.1%) and loading capacity(56.6±2.3%). The nanoparticles exhibited uniform spherical morphology, narrow size distribution (172 nm,PDI 0.17), and moderate electrostatic stability (zeta potential –27 mV). In vitro release studies demonstratedpH-dependent and controlled release of Carvacrol, with slower release under alkaline conditions, confirmingthat the albumin matrix effectively modulates compound diffusion. Stability tests conducted over 48 h at pH6.5–8.5 showed that the nanoparticles maintained their size, polydispersity, and colloidal stability.Antibacterial activity was evaluated against Aeromonas salmonicida and Listonella anguillarum, yieldinginhibition zones of 17.3 mm and 15.4 mm, and MIC values of 37.5 μg/mL and 18.75 μg/mL, respectively.Blank nanoparticles and solvent controls showed no activity, indicating that the antibacterial effect isattributed to Carvacrol. These findings demonstrate that Carvacrol retains its antibacterial efficacy afterencapsulation and that CRV-Al@NPs can provide controlled and prolonged activity against the targetpathogens. Overall, this study presents a novel nanoparticle system capable of pH-responsive controlledrelease, and the combination of natural antimicrobial compounds with nanoparticle-based delivery offers apromising and environmentally sustainable approach for disease management in aquaculture.