Caspofungin Functionalized Polymethacrylates with Antifungal Properties

Alex, Julien; Rojas, Katherine G.; Kindl, Till; Bellstedt, Peter; Weber, Christine; Heinekamp, Thorsten; Orasch, Thomas; Sanchez, Carlos Guerrero; Schubert, Ulrich S.; Brakhage, Axel A.

Abstract:

We describe the synthesis of hydrophilic poly(poly(ethylene glycol) methyl ether methacrylate) (PmPEGMA) and hydrophobic poly(methyl methacrylate) (PMMA) caspofungin conjugates by a post-polymerization modification of copolymers containing 10 mol % pentafluorophenyl methacrylate (PFPMA), which were obtained via reversible addition–fragmentation chain transfer copolymerization. The coupling of the clinically used antifungal caspofungin was confirmed and quantified in detail by a combination of 1H-, 19F- and diffusion-ordered NMR spectroscopy, UV–vis spectroscopy, and size exclusion chromatography. The trifunctional amine-containing antifungal was attached via several amide bonds to the hydrophobic PMMA, but sterical hindrance induced by the mPEGMA side chains prohibited intramolecular double functionalization. Both polymer–drug conjugates revealed activity against important human-pathogenic fungi, that is, two strains of Aspergillus fumigatus and one strain of Candida albicans (2.5 mg L–1

Year:

2020

Type of Publication:

Article

Journal:

Biomacromolecules

Volume:

21

Pages:

2104 - 2115

DOI:

https://doi.org/10.1021/acs.biomac.0c00096