Bioadhesive pH-responsive chitosan-dextran nanoparticles for controlled trimethoprim delivery in urinary tract infections.

The globally affected Urinary Tract Infections (UTI) is caused by resistant uropathogens, formation of biofilms, and intracellular persistence. In the present study, chitosan-dextran nanoparticles that are bioadhesive in nature were prepared as a nanocarrier for controlled delivery system of trimethoprim drug for enhancing the antimicrobial, antibiofilm activity against the multidrug-resistant uropathogens. Blank CS-DX NCPs and drug loaded TMP-CS-DX NCPs synthesized were subjected to FT-IR, XRD and TEM analysis to find out the possible functional groups, crystalline nature of the synthesized nanoparticles and to determine the morphology of the nanoparticles respectively. In addition, DLS measurements, zeta potential analysis, drug loading, entrapment efficiency and in vitro drug release studies were performed. The synthesized nanoparticles were used to determine the in vitro cytotoxicity and apoptosis study in HEK-293 cells. The antimicrobial efficacy and biofilm quantification were performed against Escherichia coli, Klebsiella spp and Candida albicans. Disc diffusion analysis, crystal violet-based biofilm quantification and MIC determination were analysed. From the obtained results, it is evident that the physiochemical, cellular and microbiological analysis using the drug loaded TMP-CS-DXNCPs exhibited superior antimicrobial, antibiofilm activity with minimal cytotoxicity proving their potential as a promising nano based therapeutic platform for effective management for UTI treatment.