Bacterial sepsis is a mortal syndromic disease characterized by a complex pathophysiology that hinders effective targeted therapy. This study aimed to develop multifunctional, biomimetic and pH-responsive ciprofloxacin-loaded chitosan (CS)/sodium deoxycholic acid (SDC) nanoplexes (CS/SDC) nanoplexes with the ability to target and modulate the TLR4 pathway, activated during sepsis. The formulated nanoplexes were characterized in terms of physicochemical properties, in silico and in vitro potential biological activities. The optimal formulation showed good biocompatibility and stability with appropriate physicochemical parameters. The surface charge changed from negative at pH 7.4 to positive at pH 6.0 accompanied with a significantly faster release of CIP at pH 6.0 compared to 7.4. The biomimicry was elucidated by in silico tools and MST and results confirmed strong binding between the system and TLR4. Furthermore, the system revealed 4- and 2-fold antibacterial enhancement at acidic pH, and 3- and 4-fold better antibiofilm efficacy against Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (P. aeruginosa) respectively, compared to bare CIP. In addition, enhanced bacterial efflux pump inhibition was demonstrated by CS/SDC nanoplexes. Finally, the developed nanosystem showed excellent antioxidant activity against DPPH radicals. Taken together, the study confirmed the multi-functionalities of CS/SDC nanoplexes and their potential benefits in improving bacterial sepsis therapy.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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