Development and characterization of cefazolin loaded zinc oxide nanoparticles composite gelatin nanofiber mats for postoperative surgical wounds

Systemic antibiotic therapy in post-operative wound care remain controversial leading to escalation in levels of multi-resistant bacteria with unwanted morbidity and mortality. Recently zinc (Zn) because of multiple biophysiological functions, gain considerable interest for wound care. Based on our current understanding, the present study was designed with an intent to produce improve therapeutic approaches for post-operative wound management using composite multi-functional antibiotic carrier. The study involved the fabrication, characterization and pre-clinical evaluation of cefazolin nanofiber mats loaded with zinc oxide (ZnO) and comparing co-formulated mats with individual component, enable a side by side comparison of the benefits of our intervention. Minimum inhibitory concentration (MIC) of the drug, ZnO nanoparticles (ZnONPs) and drug-ZnONP mixture against Staphylococcus aureus was determined using micro dilution assay. The fabricated nanofibers were then evaluated for in-vitro antimicrobial activity and the mechanism of inhibition was predicted by scanning electron microscopy (SEM). Further these nanofiber mats were evaluated in-vivo for wound healing efficacy in Wistar rats. Study revealed that the average diameter of the nanofibers is around 200-900 nm with high entrapment efficiency and display sustained drug release behavior. The combination of ZnO and cefazolin in 1:1 weight ratio showed higher anti-bacterial activity of 1.9 +/- 0.2 mu g/ml. Transmission electron microscopy of bacterial cells taken from the zone of inhibition revealed the phenomenon of cell lysis in tested combination related to cell wall disruption. Further composite medicated nanofiber mats showed an accelerated wound healing as compared to plain cefazolin and ZnONP loaded mats. Macroscopical and histological evaluations demonstrated that ZnONP hybrid cefazolin nanofiber showed enhanced cell adhesion, epithelial migration, leading to faster and more efficient collagen synthesis. Hence the fabricated composite nanofiber mats have the potential to be used as a postoperative antimicrobial wound dressings. (C) 2015 Elsevier B.V. All rights reserved.