Deciphering the Drug Delivery Potential of Milk Exosome Nanovesicles for Aminobenzylpenicillin Therapeutic Efficacy against Contagious Staphylococcus Aureus in Bovine Mastitis

Abstract

The emergence of antimicrobial resistance and failure of antibiotic treatment are challenging tasks for managing bovine mastitis, which is mainly caused by the contagious Staphylococcus aureus (S. aureus).To overcome these difficulties, there is an urgent need for a novel drug system. In the present study, the aim is to develop next‐generation therapeutics against S. aureus by harnessing the drug delivery potential of milk nanovesicles called milk exosomes (mENs). In the present work, a drug system is developed by encapsulating aminobenzylpenicillin (AMP) in mENs (mENs‐AMP). Electron microscopy and zeta‐sizer results indicate that the size of mENs‐AMP ranged from 55.79 ± 2.8 to 85.53 ± 7.4 nm. The AMP loading efficiency in mENs is 88.61% with its sustained release. Fluorescence spectroscopy results indicated that mENs are biocompatible with mammary epithelial cells. In vitro studies show that the antibacterial activity and the minimum inhibitory concentrations of mENs‐AMP are eleven times greater and four times lower than that of unencapsulated AMP, respectively. The mENs‐AMP exhibit significantly higher therapeutic efficacy than AMP at the same dosage and treatment frequency. Validation of this approach is demonstrated in mastitis‐affected animals through an observation in the reduction of somatic cell counts and bacterial loads in the milk of treated animals.