Fabrication of pH-Sensitive Dual Antibiotic-Loaded PVP-PEG@ZnO Nanohybrids for Controlled Drug Release to Combat Bacteria

The increasing rate of antibiotic resistance is a major threat for healthcare systems that elevate the necessity of exploring new materials to combat infectious diseases. Zinc oxide-based nanomaterials have emerged as promising candidates to minimize drug resistance due to their potential antibacterial properties and also as cargo to deliver antibiotics for sustained release. Here, we engineer zinc oxide-based colloidal hybrid system comprised of poly (ethylene glycol) (PEG) and amphiphilic poly (vinyl pyrrolidone) (PVP) as a stabilizing agent for controlled drug release. Ciprofloxacin (CF) and metronidazole (MZ) with different polarities are encapsulated in PVP-PEG@ZnO nanohybrid as model antibiotics against aerobic and anaerobic bacteria. The present study investigates the effects of the CF/MZ: ZnO nanohybrid composition ratio on encapsulation efficiency, drug release, and antimicrobial activity. For the comparison, we also synthesized PEG@ZnO incorporated enrofloxacin (EFX) (model hydrophobic drug) by a sol-gel procedure. We report that our in vitro drug release kinetics are well aligned with Ritger-Peppas and Sahlin-Peppas equations. The binding efficacy of drugs and PVP-PEG@ZnO nanohybrid was investigated using molecular dynamic simulations and DFT methods. Free energy calculations and root-mean-square deviation (RMSD) were applied to analyze binding interactions. This research will provides an insight into the engineering of ZnO-based nanomaterials for dual-drug delivery to improve infection treatment.