Introduction
The study focuses on improving the solubility and bioavailability of enrofloxacin (ENR), a third-generation quinolone antibiotic used in veterinary medicine. ENR is effective against colibacillosis and salmonellosis but suffers from poor aqueous solubility and low bioavailability, necessitating repeated dosages. This research aims to develop polymeric micelles using methoxy poly (ethylene glycol)-poly(lactide) (mPEG-PLLA) to encapsulate ENR, enhancing its solubility and antibacterial performance.
Methods
The ENR polymeric micelles (ENR-m) were prepared using a solvent evaporation method. The formulation was optimized using a Box–Behnken design (BBD) to achieve high drug loading (DL) and entrapment efficiency (EE). The physicochemical properties, in vitro drug release, pharmacokinetics, and antibacterial efficacy of ENR-m were evaluated against pure ENR.
Results
The ENR-m demonstrated satisfactory drug loading (68.38 ± 0.22%), entrapment efficiency (88.40 ± 0.91%), particle size (133.67 ± 3.10 nm), and polydispersity index (0.13 ± 0.03). The micelles exhibited excellent stability under environmental conditions and accelerated drug release in PBS solution. Pharmacokinetic studies in beagles showed that the oral bioavailability of ENR-m was enhanced by approximately 1.60-fold compared to pure ENR and by 1.66-fold compared to commercially available ENR tablets. The antibacterial activity of ENR-m against Escherichia coli and Salmonella typhi was stronger than that of pure ENR.
Discussion
ENR, known chemically as 1-cyclopropyl-7-(4-ethyl-1-piperazinyl)-6-fluoro-1,4-dihidro-4-oxo-3-quinoline carboxylic acid, is widely used in veterinary medicine. Despite its efficacy, ENR’s poor solubility limits its bioavailability, leading to repeated stress and potential drug resistance. Various technologies, including polymeric micelles, have been developed to improve drug solubility. Polymeric micelles, formed through the self-assembly of amphiphilic polymers, enhance the solubility of hydrophobic drugs and protect them from enzymatic degradation.
Materials and Preparation
ENR and mPEG-PLLA were sourced from reputable suppliers, and the micelles were prepared using a solvent evaporation method. The DL and EE of the ENR-m formulations were measured using centrifugation and HPLC. A three-factor, three-level BBD was employed to optimize the formulation, with DL and EE as dependent responses.
Characterization and Stability
The particle size and morphology of the micelles were analyzed using dynamic light scattering (DLS) and transmission electron microscopy (TEM). The micelles exhibited a spherical shape with smooth surfaces. The FT-IR spectrum confirmed the successful encapsulation of ENR within the micelles. Accelerated stability testing showed that the micelles maintained their integrity under high temperature and humidity conditions.
In Vitro and In Vivo Studies
The in vitro release of ENR from the micelles was significantly improved compared to pure ENR. Pharmacokinetic studies in beagles demonstrated enhanced bioavailability and peak plasma concentrations for ENR-m. The antibacterial activity of ENR-m was superior to that of pure ENR, as evidenced by larger inhibition zones against E. coli and S. typhi.
Optimization and Analysis
The BBD optimization process identified the optimal formulation conditions for ENR-m. The response surface analysis revealed the significant effects of polymer concentration, water-to-oil ratio, and feed ratio on DL and EE. The optimized formulation showed no significant difference between predicted and experimental values, validating the optimization process.
Conclusion
The study successfully developed ENR-m using mPEG-PLLA, enhancing the solubility, bioavailability, and antibacterial efficacy of ENR. The findings suggest that polymeric micelles are a promising drug delivery system for veterinary applications, offering improved therapeutic outcomes and reduced environmental impact.
🔗 **Fuente:** https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2025.1595137/full