Stimulus Responsive Ocular Gentamycin-Ferrying Chitosan Nanoparticles Hydrogel: Formulation Optimization, Ocular Safety and Antibacterial Assessment

Nabil K Alruwaili,1 Ameeduzzafar Zafar,1 Syed Sarim Imam,2 Khalid Saad Alharbi,3 Nasser Hadal Alotaibi,4 Sultan Alshehri,2,5 Nabil A Alhakamy,6 Abdulaziz I Alzarea,1 Muhammad Afzal,3 Mohammed Elmowafy1,7 1Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Kingdom of Saudi Arabia; 2Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia; 3Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Kingdom of Saudi Arabia; 4Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Kingdom of Saudi Arabia; 5College of Pharmacy, Almaarefa University, Riyadh, Kingdom of Saudi Arabia; 6Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 7Department of Pharmaceutics and Ind. Pharmacy, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, EgyptCorrespondence: Ameeduzzafar Zafar Email zzafarpharmacian@gmail.comPurpose: The present study was designed to study the gentamycin (GTM)-loaded stimulus-responsive chitosan nanoparticles to treat bacterial conjunctivitis.Methods: GTM-loaded chitosan nanoparticles (GTM-CHNPs) were prepared by ionotropic gelation method and further optimized by 3-factor and 3-level Box–Behnken design. Chitosan (A), sodium tripolyphosphate (B), and stirring speed (C) were selected as independent variables. Their effects were observed on particle size (PS as Y1), entrapment efficiency (EE as Y2), and loading capacity (LC as Y3).Results: The optimized formulation showed the particle size, entrapment efficiency, and loading capacity of 135.2± 3.24 nm, 60.18± 1.65%, and 34.19± 1.17%, respectively. The optimized gentamycin-loaded chitosan nanoparticle (GTM-CHNPopt) was further converted to the stimulus-responsive sol-gel system (using pH-sensitive carbopol 974P). GTM-CHNPopt sol-gel (NSG5) exhibited good gelling strength and sustained release (58.99± 1.28% in 12h). The corneal hydration and histopathology of excised goat cornea revealed safe to the cornea. It also exhibited significant (p< 0.05) higher ZOI than the marketed eye drop.Conclusion: The finding suggests that GTM-CHNP-based sol-gel is suitable for ocular delivery to enhance the corneal contact time and improved patient compliance.Keywords: chitosan, nanoparticles, gentamycin, histopathology, antimicrobial assessment, HET CAM test