Biogenic Silver Nanoparticles from Penicillium chrysogenum Incorporated in Polymeric Micelles: Antimicrobial Activity and Cytotoxicity Evaluation

Abstract Biogenic silver nanoparticles (AgNPs) are investigated for their antimicrobial activity and reduced toxicity associated with metabolite-derived surface coatings. Their stability and biological activity are enhanced by metabolite-derived coatings produced by the synthesizing organism. This study develops hybrid nanocarriers by combining biogenic AgNPs synthesized from Penicillium chrysogenum with poloxamer micelles. Subsequently, the AgNPs were incorporated into poloxamer-based micelles (PL188 and PL407), yielding the nanocarriers AgNPs_PL407 and AgNPs_PL188. Physicochemical characterization was performed using dynamic light scattering (DLS) to determine hydrodynamic diameter (Dh), polydispersity index (PDI), and zeta potential (ζ). Antimicrobial activity was evaluated through disk-diffusion assays, minimum inhibitory concentration (MIC), and bacterial growth kinetics. Cell viability was assessed using trypan blue exclusion and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assays. Biogenic AgNPs exhibited a Dh of 277.20 ± 112.16 nm, a PDI of 0.271, and a ζ potential of −9.40 ± 0.54 mV. Pure poloxamers showed ζ potentials close to zero (0.03 ± 0.07 mV and −0.01 ± 0.06 mV, respectively). Incorporation resulted in AgNPs_PL407 nanocarriers, characterized by greater heterogeneity, with a Dh of 555.60 ± 268.40 nm and a PDI of 1.000, and in AgNPs_PL188 nanocarriers, characterized by greater homogeneity, with a Dh of 301.63 ± 106.11 nm and a PDI of 0.349. Both hybrid systems exhibited ζ potentials near zero (−0.02 ± 0.00 mV for AgNPs_PL407 and −0.00 ± 0.00 mV for AgNPs_PL188), indicating the possible colloidal stabilization conferred by the poloxamers. Both the AgNPs and the hybrid nanocarriers demonstrated antimicrobial activity across the tested combinations, supporting their broad antimicrobial potential. Importantly, most antimicrobial MIC values were below the cytotoxicity threshold determined for HaCaT cells (IC50 = 2.29 × 1010 NPs/mL), particularly those obtained for the hybrid nanocarriers. However, free AgNPs against E. coli showed an MIC of 2.65 × 1010 NPs/mL, slightly exceeding the HaCaT IC50, indicating that the apparent therapeutic window was formulation- and microorganism-dependent. Cytotoxicity assays also confirmed high cell viability at biologically active concentrations, particularly for the hybrid systems. AgNPs_PL188 showed the most promising overall profile, combining favorable antibacterial performance with low apparent cytotoxicity. Overall, these results suggest that incorporating biogenic AgNPs into poloxamer micelles may improve their apparent antimicrobial selectivity over cytotoxicity, highlighting their potential for developing antimicrobial formulations, particularly for oral inhalation administration. However, further studies are needed to optimize the system and ensure product safety.