Caspofungin Functionalized Polymethacrylates with Antifungal Properties

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 1 H-, 19 Fand 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 < MEC < 8 mg L −1 , MIC 50 = 4 mg L −1 ), whereas RAW 264.7 macrophages as well as HeLa cells remained unaffected at these concentrations.

Nanogels as Antifungal‐Drug Delivery System Against Aspergillus Fumigatus

“…Biofilm Formation and Quantification: Biofilms were formed by adding 100 μL of A. fumigatus spore suspension in RPMI 1640 medium (2 Â 10 5 spores mL À1 ) to 100 μL of drug or drug-loaded NGs in the same medium for different time points (6,24, and 48 h). Wells were then washed with PBS and fixed with 4% paraformaldehyde and left to air dry.…”

“…[ 5 ] One recently published and interesting approach is the generation of prodrug–nanoparticles with antifungal properties. [ 6 ]…”

“…[5] One recently published and interesting approach is the generation of prodrug-nanoparticles with antifungal properties. [6] Nanoparticulate hydrogels better known as nanogels (NGs) are considered as promising vehicles in drug delivery because of their biocompatibility, high water content, control over drug release, and loading capacity for both amphiphilic and hydrophobic drugs. [7] We have previously reported the synthesis of disulfide crosslinked poly(glycidol) (pG)-based NGs by inverse miniemulsion.…”

Antifungal polymers for medical applications

“…glabrata ; additionally, the materials showed biocompatibility (Michl, Giles, Cross, et al, 2017). More recently, caspofungin has been grafted onto polymethacrylates (Alex et al, 2020) such as poly(2‐hydroxyethylmethacrylate) (PHEMA) (Michl, Giles, Mocny, et al, 2017) for antifungal activity against Candida and Aspergillus species.…”

Simultaneous Grafting Polymerization of Acrylic Acid and Silver Aggregates Formation by Direct Reduction Using γ Radiation onto Silicone Surface and Their Antimicrobial Activity and Biocompatibility

“…One of the most common strategies to provide antimicrobial activity to surfaces (e.g., carbon nanomaterials [ 7 , 8 ], inorganic substrates [ 9 , 10 ], and polymeric substrates [ 11 ]) is the immobilization of antimicrobial agents through interactions between the antimicrobials and grafted polymer chains onto the base material or by covalent attachment of the antimicrobial to the surface of the base material [ 12 , 13 ]. These antimicrobial agents may be both organic (classical molecular antibiotics) or inorganic (metallic particles) in nature; however, the latter have attracted more attention because the use of classical antibiotics still increase concerns for bacterial antibiotic resistance [ 14 , 15 ]. Most inorganic antimicrobial compounds are metal salts or metal nanoparticles, such as those containing copper, titanium, zinc, and silver, whose biggest advantage is the fact that they can not only be used by themselves, but they can also be combined onto organic substrates such as polymers, or even work alongside other antimicrobials on complicated substrates.…”