The emergence of antibiotic-resistant bacteria has created a global health crisis, with bacterial infections now ranking as the second leading cause of death worldwide. This situation underscores the need for sustainable antibiotic nanoformulations. In response, we developed a Generally Recognized As Safe (GRAS) polyphenol-polymer nanoparticle (PNP) system for drug delivery. This study aims to optimize PNPs for the encapsulation and delivery of oxytetracycline (OTC) complexed with magnesium and calcium ions to improve its in vitro activity against human pathogens. OTC-loaded PNPs were synthesized via Flash Nanoprecipitation (FNP) method and the loaded nanoparticles were characterized using UV-vis, Fluorescence, Fourier-Transformed Infrared (FT-IR) spectroscopy, which confirmed the presence of OTC in the PNPs system. The synthesis method was optimized to achieve consistent and high encapsulation efficiencies. The hydrodynamic size of the loaded particles was measured through Dynamic Light Scattering (DLS) and demonstrated sub-micron size particles in suspension. The antimicrobial potency of the formulation was evaluated against Escherichia coli K-12 and Staphylococcus aureus. Preliminary checkerboard assays demonstrated that the interaction of divalent cations with OTC did not interfere with its antibacterial activity. More so, OTC-loaded PNPs demonstrated enhanced sustained and inhibitory effects compared to free OTC as observed in Minimum Inhibitory Concentration (MIC) and Time-kill assays. Cytotoxicity and biocompatibility assessments on Murine Macrophages and Human Dermal Fibroblasts are also underway. Overall, this approach aims to improve OTC stability and efficacy through controlled release, potentially reducing antibiotic resistance and decreasing the frequency of administration, thereby offering a sustainable antimicrobial strategy.

Cecilia Ezeanya

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