pH‐driven entrapment of enrofloxacin in casein‐based nanoparticles for the enhancement of oral bioavailability.

Enrofloxacin (ENR), a broad‐spectrum antibacterial drug, has extremely poor water solubility contributing to low bioavailability, which prevents drug formulation design and limits its wide application in livestock farming and aquaculture. Compared to conventional formulations of ENR, casein (Cas)‐based drug delivery system has been reported to have significant advantages in the improvement of solubility and bioavailability of drugs. In this paper, we report the preparation process of ENR‐loaded Cas nanoparticles (ENR‐Cas) using magnetic agitation without any organic agent and the optimization of the formulation. Transmission electron microscopy (TEM), dynamic light scattering (DLS), differential scanning calorimetry (DSC), powder X‐ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR) were all adopted to characterize the ENR‐Cas. Results showed that the obtained ENR‐Cas were approximately spherical with a particle size of 171.6 ± 13.8 nm with a polydispersity index of 0.322 ± 0.053. In vitro release behavior of ENR‐Cas showed a sustained release profile. Additionally, in vivo study in rats displayed that the mean plasma concentration of ENR after oral administration of ENR‐Cas was significantly higher than that treated with ENR suspension. The mean residence time (MRT0–24) of ENR was enhanced by Cas nanoparticles from 9.287 ± 0.524 to 11.372 ± 1.139 hr in comparison with ENR suspension. Accordingly, the area under the curve (AUC0–24) of ENR‐Cas was 80.521 ± 6.624 μg·hr/ml, 3.8‐fold higher than that of ENR suspension (20.850 ± 1.715 μg·hr/ml). Therefore, it can be concluded that ENR‐Cas enhanced the absorption, prolonged the retention time, and improved oral bioavailability of ENR. Taken the good oral safety of Cas into consideration, ENR‐Cas should be a more promising oral preparation of ENR for clinical application. [ABSTRACT FROM AUTHOR]