Enhancing the Solubility and Antibacterial Efficacy of Sulfamethoxazole by Incorporating Functionalized PLGA and Graphene Oxide Nanoparticles into the Crystal Structure

Background/Objectives: The widespread use of sulfamethoxazole (SMX) has led to increasing antibiotic resistance, and there is a need for improved formulations to enhance its therapeutic effectiveness. In this study, we investigated the biocidal potential of SMX composite crystals incorporated with functionalized poly(lactic-co-glycolic acid) (nfPLGA) and nano-graphene oxide (nGO). Methods: The composites, namely SMX-nfPLGA and SMX-nGO, were synthesized via antisolvent precipitation and evaluated using Kirby–Bauer disk diffusion assays. Results: Incorporation of nfPLGA and nGO significantly improved SMX solubility, increasing it from 0.029 mg/mL to 0.058 mg/mL and 0.063 mg/mL, respectively. Additionally, the log partition coefficient (log P or K_w) also improved from 1.4 to 0.86 for nGO and 0.92 for nfPLGA composites. Both formulations exhibited improved antibacterial activity with distinct time-dependent bactericidal effects. Compared to pure SMX, the SMX-nfPLGA showed 60% and 53% greater bacterial inhibition at concentrations of 50 mg/mL and 100 mg/mL, respectively. Although SMX-nGO was slightly less potent, it still surpassed pure SMX, with 50% and 33% higher inhibition at the same concentrations. Conclusions: Importantly, neither nfPLGA nor nGO showed any biocidal effects, confirming that the observed enhancement was due to improved SMX solubility caused by their incorporation. These findings suggest that embedding solubility-enhancing nanoparticles into the existing crystal structure of the antibiotic is a promising strategy for enhancing the effectiveness.