Theranostic antibacterial agents based on biodegradable polymer nanoarchitectures

Abstract

Infections caused by bacteria and other microbes are continued to be one of the most challenging problems that requires continuous attention of the scientific community in handling the healthcare of the society at large. Currently, beta-lactam antibiotics (like Penicillin) are used as clinical drugs for the treatment of bacterial infections; however, unprecedent mutations in microbes quickly develop high resistance against majority of these antibiotic drugs. Antimicrobial peptides are seen as a nature s selection for treating bacterial infectious; however, tedious multi-step synthesis for large scale production, hemolytic side effects and in vivo toxicity pose huge challenge for AMPs long-term feasibility in therapeutics. In order to circumvent this challenge, synthetic cationic polymers are emerging as a new alternative in the treatment of both gram-negative and gram-positive bacterial infectious strains. This thesis work is primarily focused to design and develop cationic biodegradable polymer as theranostic agents-cum-probe for simultaneous visualization and quantitative determination of antibacterial activity as well as to understand the role of polymeric architectural aspects like topology, charge and hydrophobicity for the treatment of bacterial infections. A new class of cationic polycaprolactone (PCL) was tailor-made which was extremely selective towards Gram-negative bacterium Escherichia coli (E. coli) as compared to mice red blood cells (RBC) and wild-type mouse embryonic fibroblast (WT-MEF) cells with a selectivity index gt104. Polymeric adherence on the surface of E. coli membrane was confirmed by reduction in magnitude of E. coli surface charge potential. It was attributed to the electrostatic interaction between the anionic membrane and cationic PCL polymer. Anionic biomarker 8-hydroxy-pyrene-1,3,6-trisulfonic acid (HPTS) was loaded in the cationic PCL NP via electrostatic interaction to yield a new fluorescent theranostic nanoprobe to accomplish both therapeutics and diagnostics together