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Side Chain Degradable Cationic-amphiphilic Polymers with Tunable Hydrophobicity Show In-vivo Activity

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Title Side Chain Degradable Cationic-amphiphilic Polymers with Tunable Hydrophobicity Show In-vivo Activity
Not Available
 
Creator Uppu DSSM
Samaddar S
Hoque J
Konai MM
Krishnamoorthy P
Shome BR
Haldar J
 
Subject Polymers, In Vivo activity
 
Description Not Available
Cationic–amphiphilic antibacterial polymers with optimal amphiphilicity generally target the bacterial membranes instead of mammalian membranes. To date, this balance has been achieved by varying the cationic charge or side chain hydrophobicity in a variety of cationic–amphiphilic polymers. Optimal hydrophobicity of cationic–amphiphilic polymers has been considered as the governing factor for potent antibacterial activity yet minimal mammalian cell toxicity. However, the concomitant role of hydrogen bonding and hydrophobicity with constant cationic charge in the interactions of antibacterial polymers with bacterial membranes is not understood. Also, degradable polymers that result in nontoxic degradation byproducts offer promise as safe antibacterial agents. Here we show that amide- and ester (degradable)-bearing cationic–amphiphilic polymers with tunable side chain hydrophobicity can modulate antibacterial activity and cytotoxicity. Our results suggest that an amide polymer can be a potent antibacterial agent with lower hydrophobicity whereas the corresponding ester polymer needs a relatively higher hydrophobicity to be as effective as its amide counterpart. Our studies reveal that at higher hydrophobicities both amide and ester polymers have similar profiles of membrane-active antibacterial activity and mammalian cell toxicity. On the contrary, at lower hydrophobicities, amide and ester polymers are less cytotoxic, but the former have potent antibacterial and membrane activity compared to the latter. Incorporation of amide and ester moieties made these polymers side chain degradable, with amide polymers being more stable than the ester polymers. Further, the polymers are less toxic, and their degradation byproducts are nontoxic to mice. More importantly, the optimized amide polymer reduces the bacterial burden of burn wound infections in mice models. Our design introduces a new strategy of interplay between the hydrophobic and hydrogen bonding interactions keeping constant cationic charge density for developing potent membrane-active antibacterial polymers with minimal toxicity to mammalian cells.
Not Available
 
Date 2018-09-15T09:28:33Z
2018-09-15T09:28:33Z
2016-07-21
 
Type Research Paper
 
Identifier Biomacromolecules 17, 9, 3094-3102
1525-7797
http://krishi.icar.gov.in/jspui/handle/123456789/6899
 
Language English
 
Relation Not Available;
 
Publisher American Chemical Society Publications