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Chitosan derivatives active against multi-drug resistant bacteria and pathogenic fungi: In vivo evaluation as topical antimicrobials

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Title Chitosan derivatives active against multi-drug resistant bacteria and pathogenic fungi: In vivo evaluation as topical antimicrobials
Not Available
 
Creator Hoque J
Adhikary U
Yadav V
Samaddar S
Konai MM
Prakash RG
Krishnamoorthy P
Shome BR
Sanyal K
Haldar J
 
Subject antimicrobial polymer; antimicrobial resistance; cationic chitosan derivatives; drug-sensitive and drug-resistant bacteria; pathogenic fungi; topical infection
 
Description Not Available
The continuous rise of antimicrobial resistance and the dearth of new antibiotics in the clinical pipeline raise an urgent call for the development of potent antimicrobial agents. Cationic chitosan derivatives, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chlorides (HTCC), have been widely studied as potent antibacterial agents. However, their systemic structure–activity relationship, activity toward drug-resistant bacteria and fungi, and mode of action are very rare. Moreover, toxicity and efficacy of these polymers under in vivo conditions are yet to be established. Herein, we investigated antibacterial and antifungal efficacies of the HTCC polymers against multidrug resistant bacteria including clinical isolates and pathogenic fungi, studied their mechanism of action, and evaluated cytotoxic and antimicrobial activities in vitro and in vivo. The polymers were found to be active against both bacteria and fungi (MIC = 125–250 μg/mL) and displayed rapid microbicidal kinetics, killing pathogens within 60–120 min. Moreover, the polymers were shown to target both bacterial and fungal cell membrane leading to membrane disruption and found to be effective in hindering bacterial resistance development. Importantly, very low toxicity toward human erythrocytes (HC50 = >10000 μg/mL) and embryo kidney cells were observed for the cationic polymers in vitro. Further, no inflammation toward skin tissue was observed in vivo for the most active polymer even at 200 mg/kg when applied on the mice skin. In a murine model of superficial skin infection, the polymer showed significant reduction of methicillin-resistant Staphylococcus aureus (MRSA) burden (3.2 log MRSA reduction at 100 mg/kg) with no to minimal inflammation. Taken together, these selectively active polymers show promise to be used as potent antimicrobial agents in topical and other infections.
Not Available
 
Date 2018-09-15T09:30:06Z
2018-09-15T09:30:06Z
2016-09-02
 
Type Research Paper
 
Identifier Mol. Pharmaceutics 13, 10, 3578-3589
1543-8384
http://krishi.icar.gov.in/jspui/handle/123456789/6905
 
Language English
 
Relation Not Available;
 
Publisher American Chemical Society Publications