Development and evaluation of mPEG-PLLA polymeric micelles encapsulating enrofloxacin for enhanced solubility, bioavailability, and antibacterial performance.

Abstract

The aim of this study was to prepare polymeric micelles composed of enrofloxacin (ENR) and methoxy poly (ethylene glycol)-poly(lactide) (mPEG-PLLA) using a solvent evaporation method to overcome the solubility-limited oral bioavailability of ENR. The formulation was optimized using a Box-Behnken design (BBD) to obtain ENR polymeric micelles (ENR-m) with high drug loading (DL, %) and entrapment efficiency (EE, %). The physicochemical properties,drug release, pharmacokinetics, and antibacterial efficacy were evaluated in comparison to pure ENR. ENR-m was successfully prepared and demonstrated satisfactory drug loading (68.38&#x202f;&#xb1;&#x202f;0.22%), entrapment efficiency (88.40&#x202f;&#xb1;&#x202f;0.91%), particle size (PS) (133.67&#x202f;&#xb1;&#x202f;3.10&#x202f;nm), and polydispersity index (PDI) (0.13&#x202f;&#xb1;&#x202f;0.03). The ENR-m also exhibited excellent stability under environmental conditions (40&#xb0;C and 75% relative humidity (RH)).release of ENR from micelles was accelerated in a PBS solution. A pharmacokinetic study on beagles revealed that the oral bioavailability of ENR-m was enhanced by approximately 1.60-fold compared to pure ENR (&#x202f;<&#x202f;0.01) and by 1.66-fold compared to commercially available tablets of ENR (&#x202f;<&#x202f;0.01). The antibacterial activity of ENR-m against() and() was stronger than that of pure ENR.