Branched amphotericin functional poly(N- iso propyl acrylamide): an antifungal polymer

支链两性霉素功能化聚(N-异丙基丙烯酰胺):一种抗真菌聚合物

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作者:Thomas Swift, Emily Caseley, Abbigail Pinnock, Joanna Shepherd, Nagaveni Shivshetty, Prashant Garg, C W Ian Douglas, Sheila MacNeil, Stephen Rimmer

Abstract

Branched poly(N-isopropylacrylamide) was functionalized with Amphotericin B (AmB) at the chain ends to produce an antifungal material. The polymer showed antifungal properties against AmB-sensitive strains of Candida albicans, Fusarium keratoplasticum and Aspergillus flavus (minimal inhibitory concentration ranged from 5 to 500 µg ml-1) but was not effective against an AmB resistant strain of C. albicans nor against Candida tropicalis. The polymer end groups bound to the AmB target, ergosterol, and the fluorescence spectrum of a dye used as a solvatochromic probe, Nile red, was blue shifted indicating that segments of the polymer became desolvated on binding. The polymer was less toxic to corneal and renal epithelial cells and explanted corneal tissue than the free drug. Also, the polymer did not induce reactive oxygen species release from peripheral blood mononuclear cells, nor did it cause a substantial release of the proinflammatory cytokines, tumour necrosis factor-α and interleukin-1β (at 0.5 mg ml-1).

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