ORCID

0009-0005-5517-0255

Keywords

Metal Complexation, Controlled Release, Flash Nanoprecipitation, Sustainable Antimicrobial Strategy, Repurposing Antibiotics, Biomedical and Agricultural Use

Abstract

While nanotechnology enables sustainable antibiotic delivery by reducing drug dosage without compromising efficacy, reliable nanocarrier systems for antibiotics remain scarce, in part due to the physicochemical properties of the drug. Oxytetracycline (OTC), a widely used antibiotics in agriculture and biomedicine, is unstable at pH above 2. Although complexation with divalent cations like calcium and magnesium at pH above 6 improves its stability, the resulting hydrophobicity may limit release. To address this, we optimized OTC-divalent cation complexation and encapsulated the complexes within our Generally Recognized as Safe (GRAS) polyphenol polymeric nanoparticles (PNP), which served as the nanocarrier. The particles were synthesized via flash nanoprecipitation and characterized using UV-Vis, fluorescence, Fourier-transformed Infrared (FT-IR), Liquid Chromatography -Mass Spectrometry (LC-MS), and Scanning Electron Microscopy (SEM) to confirm OTC encapsulation. DLS showed an increase in sub-micron hydrodynamic size of OTC-loaded PNP (OPNP) compared to PNP, indicating successful OTC loading. Checkerboard assay demonstrated that complexation didn’t significantly interfere with OTC’s potency. Disk diffusion and MIC assays revealed comparable inhibition between free OTC and OPNP. Notably, MIC after 10 hours in vitro release showed that OPNP maintained antibacterial action against E. coli k12 and S. aureus, unlike free OTC. Time-kill assay showed that E. coli k12 responded rapidly, while S. aureus required prolonged exposure. Toxicity assays on Citrus sinensis (sweet orange) showed no adverse effects at 200µg/mL, and interestingly OPNP remained on the leaves after simulated rain. Non-toxicity at ≤16ug/mL of treatment on murine macrophage was observed. These findings suggest that OPNP is a sustainable, non-toxic formulation with suitable size and sustained release, enabling both curative and preventive antibacterial activity against potential plant and skin infections.

Completion Date

2025

Semester

Summer

Committee Chair

Swadeshmukul Santra

Degree

Master of Science (M.S.)

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Format

PDF

Release Date

8-15-2027

Document Type

Thesis

Campus Location

Orlando (Main) Campus

Subjects

Antibacterial agents--Controlled release; Oxytetracycline; Antibacterial agents--Research; Polymeric drug delivery systems; Nanocapsules

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