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Green Synthesis of Ciprofloxacin-Loaded Cerium Oxide/Chitosan Nanocarrier and its Activity Against MRSA-Induced Mastitis
Affiliation:1. Department of Biological Sciences, International Islamic University, Islamabad, Pakistan;2. School of Chemical and Materials Engineering, National University of Sciences and Technology, Islamabad, Pakistan;3. Departments of Nanomedicine, California Innovations Corporation, San Diego, CA, USA;4. University of Engineering and Technology, University Lahore, Lahore, Punjab, Pakistan;5. Department of Pharmacy, Gomal University, Dera Ismail Khan, Khyber Pakhtunkhwa, Pakistan;6. College of Pharmaceutical Sciences, Soochow University, Suzhou, PR China
Abstract:Methicillin-resistant Staphylococcus aureus (MRSA)-induced mastitis is one of the biggest animal welfare issues and economic burdens worldwide. As a possible effective treatment, ciprofloxacin (CIP)-loaded cerium oxide (CeO2)/chitosan (CS) nanocomposite was synthesized using an eco-friendly approach, characterized, and evaluated. From 350 mastitis-positive milk samples, 35 mecA-positive MRSA strains were confirmed by antibiotic sensitivity testing and PCR. CeO2 nanoparticles (NPs) were synthetized using the seeds’ extract of Amomum subulatum (aka black cardamom/BC) as a reducing and capping agent, which was conjugated with CS by ionic gelation before CIP was nanoencapsulated. The resulting NPs were characterized physically (by using FESEM, TEM, EDS, XRD, FTIR, ZP, and UV-Vis spectrophotometry), biologically and pharmacologically (through in-vitro/ex-vivo antibacterial, cytotoxic, and drug release behavior assays). The CIP-nanocomposite was represented by pure, stable, small, pseudospherical NPs of crystalline nature. FTIR confirmed the surface linkage of CS and CIP in CeO2 NPs. CIP-CeO2/CS nanocarrier exerted enhanced antibacterial activity at lower MIC (8 μg/mL) compared to that of free CIP drug alone. Also, they were hemocompatible and not hepatotoxic. CIP release from the nanocarrier was better sustained in physiological-like conditions. Taken together, the phytogenic CIP-CeO2/CS nanocarrier could be considered as a potent and safe therapeutic solution for MRSA-induced mastitis.
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