Telechelic Poly(2-oxazoline)s with a Biocidal and a Polymerizable Terminal as Collagenase Inhibiting Additive for Long-Term Active Antimicrobial Dental Materials

Abstract

Although modern dental repair materials show excellent mechanical and adhesion properties, they still face two major problems: First, any microbes that remain alive below the composite fillings actively decompose dentin and thus, subsequently cause secondary caries. Second, even if those microbes are killed, the extracellular proteases such as MMP, remain active and can still degrade collagenousdental tissue. In order to address both problems, a poly(2-methyloxazoline) with a biocidal quaternary ammonium and a polymerizable methacrylate terminal was explored as additive for a commercial dental adhesive. It could be demonstrated that the adhesive rendered the adhesive contact-active antimicrobial against S. mutans at a concentration of only 2.5 wt% and even constant washing with water for 101 days did not diminish this effect. Increasing the amount of the additive to 5 wt% allowed killing S. mutans cells in the tubuli of bovinedentin upon application of the adhesive. Further, the additive fully inhibited bacterial collagenase at a concentration of 0.5 wt% and reduced human recombinant collagenase MMP-9 to 13% of its original activity at that concentration. Human MMPs naturally bound to dentin were inhibited by more than 96% in a medium containing 5 wt% of the additive. Moreover, no adverse effect on the enamel/dentine shear bond strength was detected in combination with a dental composite.

Entropically driven Polymeric Enzyme Inhibitors by End‐Group directed Conjugation

“…Besides modifying the polymer backbone, the polymer end group can be used to couple inhibitors to macromolecules. Human matrix metalloproteinases (MMPs) such as collagenase are inhibited by telechelic poly(2‐oxazolines) with N , N ‐dimethyldodecylammonium (DDA) as end groups, which were used for application in dental adhesives . Furthermore, the bacterial topoisomerase II and IV inhibitor ciprofloxacin and the transpeptidase inhibitor penicillin were attached to poly(2‐oxazolines).…”

“…Human matrix metalloproteinases (MMPs) such as collagenase are inhibited by telechelic poly(2-oxazolines) with N,N-dimethyldodecylammonium( DDA) as end groups,w hich were used for applicationi nd ental adhesives. [9] Furthermore,t he bacterial topoisomerase II and IV inhibitor ciprofloxacina nd thet ranspeptidase inhibitor penicillin were attached to poly(2-oxazolines).T his changed the activityp rofiles of the antibioticsa nd increased the hydrolysis stability against penicillinased egradation in cases of the penicillin conjugates. [10,11] One example for the third class are chitinase inhibitors that are oligo-or polysaccharides with specific binding to the active site of the enzyme.…”

Polymer‐Based Surfaces Designed to Reduce Biofilm Formation: From Antimicrobial Polymers to Strategies for Long‐Term Applications

“…There are various examples of antibiotics that have thus been surface‐immobilized using PEG spacers . Other polymers and surface architectures were also used to present covalently attached antimicrobial components (e.g., antimicrobial peptides or quaternary ammoinium compounds) …”

Poly(2‐oxazoline)s with a 2,2′‐Iminodiacetate End Group Inhibit and Stabilize Laccase

“…There are studies that show the potential of POx derivatives as inhibitors. For example, human matrix metalloproteinases (MMPs), such as collagenase, are inhibited by telechelic POx terminated with N , N ‐dimethyldodecylammonium (DDA) as end groups for use in dental adhesives . The two antibiotics ciprofloxacin and penicillin, which are both enzyme inhibitors, were shown to be active as end groups of POx .…”

“…For example, human matrix metalloproteinases (MMPs), such as collagenase, are inhibited by telechelicP Ox terminated with N,N-dimethyldodecylammonium (DDA) as end groups for use in dental adhesives. [16] The two antibiotics ciprofloxacin and penicillin, whicha re both enzyme inhibitors, were shown to be active as end groups of POx. [17] POxw ith a2 ,2'iminodiacetate (IDA) end group was previously reported to diminish the activity of HRP as an entropically driven noncompetitive inhibitor.…”