Construction of pH-responsive Thanatin nano-antibacterial drug and its inhibitory activity on NDM-1 enzyme producing drugresistant bacteria
Objective To design a nano-drug delivery system to solve the limitation that the antimicrobial peptide Thanatin cannot be used to treat systemic infectious diseases because of its poor bioavailability by intravenous injection. Methods A phenylboronic acid and orthoester functionalized chitosan block polymer was prepared using chitosan as the basic skeleton for encapsulating hydrophilic Thanatin. Results Thanatin was effectively encapsulated by nitrogen-boron coordination,and a nano-drug with a particle size of 190.8 nm,an encapsulation efficiency of 73.2％ and a drug loading of 11.6％ was obtained. The nano-drug had low cytotoxicity. The half-release time in PBS with pH of 5.5 and 6.5 was 10 min and 25 min respectively. Meanwhile,the cumulative release rate was over 90％. Compared with free Thanatin,the therapeutic efficacy of Thanatin nano-drug on septic mice caused by new delhi metallo-β-lactamase-1 (NDM-1)-producing Escherichia coli infection was significantly enhanced. Conclusion Nano-encapsulation of Thanatin can enhance circulatory stability,thus improving the therapeutic efficacy on septic mice.
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维普
