Development and Evaluation of Oral Amikacin Formulations: Enhancing Bioavailability Through Nanoparticle and Copolymer‑Mediated Delivery

Abstract

Amikacin is a broad spectrum aminoglycoside antibiotic traditionally administered parenterally due to its high hydrophilicity, poor intestinal permeability, and efflux by intestinal transporters, resulting in negligible oral bioavailability. These limitations restrict outpatient use and negatively affect patient compliance. Recent advances in drug delivery technologies, including nanoparticulate carriers and P‑glycoprotein (P‑gp) inhibition strategies, have demonstrated potential for transforming amikacin into an orally deliverable antibiotic. This study investigated two novel oral delivery platforms for amikacin: poly(D, L‑lactide‑co‑glycolide) (PLGA) nanoparticles and thiolated chitosan‑functionalized lipidic hybrids with P‑gp inhibition. Both formulations were optimized using Box–Behnken design and assessed for particle size distribution, drug loading, intestinal permeability (ex vivo), and in vivo oral bioavailability in rodent models. PLGA nanoparticles averaged ~260 nm with moderate drug loading, exhibiting enhanced intestinal uptake via Peyer’s patches. Thiolated chitosan hybrids demonstrated significant P‑gp inhibition and increased permeation parameters. In vivo pharmacokinetics revealed oral bioavailability up to ~68.6% with thiolated chitosan hybrids versus negligible absorption with unmodified amikacin. Statistical analysis (ANOVA; p < 0.05) confirmed significant improvements in serum concentrations and area under the curve (AUC) for both formulations compared to controls. These innovative delivery systems suggest that oral amikacin, previously unfeasible, can achieve therapeutically relevant systemic exposure, improving compliance and expanding clinical utility. Future work should explore human translational studies and safety profiling.