Self-deactivating biocidal polymers
Final Report Abstract
The goal of this project was to design a biocidal polymer, which exhibits a broad antimicrobial spectrum of activity and which will be fully deactivated in a desired timeframe after its application. Therefore, the nature of the polymer backbone such as the biocidal end groups was varied and finally a complete new polymer was synthesized to address the aspired requirements. At first the polymer backbone was varied and it has been shown that a PEtOx backbone, along with a PEtOx-PMOx statistical copolymer, were the best suited polymers in order to enhance the antimicrobial effect of the biocidal polymers. The resulting very high antimicrobial activities (1 µg-mL^-1) are in the top range of polymeric biocides. These polymers could also be deactivated by cleaving a single bond located at the satellite end group leading to hardly active antimicrobial polymers. The biocidal end groups were displaced with other alkylammonium end groups without gaining enhanced activities as well as deactivation rates. Moreover, all these systems suffer from their inefficiency against Gram-negative bacterial strains. Therefore, the biocidal end groups were displaced by antibiotics such as ciprofloxacin or penicillin. After a successful conjugation to the poly(2-oxazolines) they showed a very impressing antimicrobial activity, that in some cases even surpassed the molar activity of pristine ciprofloxacin. Using these antibiotic functional end groups of the polymers an antimicrobial activity against Gram-negative strains was introduced. In the case of penicillin, the conjugation to the polymer had another very impressing effect. The polymer shielded the antibiotic from an attack of penicillinase, that is present in penicillin resistant bacteria strains. Therefore, the polymer activated penicillin in the presence of the enzyme. In order to deactivate the polymers they were combined with ABA triblock copolymers and arranged during a precipitating step so that the formed aggregates showed a 500 times reduced antimicrobial activity. By a polymer analogous hydrolyzation of the end groups of the ABA triblock copolymers the aggregates can then be transformed to micelles resulting in a complete recovery of the initial antimicrobial potential. This system lacks from the relative complex deactivation method and the fact this system actually only can be activated instead of deactivated. Due to the lack of efficiency against Gram-negative strains, poly(2-oxazolines) were replaced by another polymer. Therefore hydrophilic polycations were chosen, because they in general show a good broad band biocidal activity and almost no hemolytic activity. In order to prove the potential of these polymers poly(2-methyl-2-oxazolines) were hydrolyzed in order to gain linear polyethyleneimines. They show a good activity against Gram-positive as well Gram-negative bacterial strains and the revealed a molecular weight dependent activity as well. This was also been found by Strassburg for hydrophilic polycations. Polymers with a high molecular weight (3000-5000 g-mol^-1) showed good antimicrobial performance whereas oligomers below 1000 g-mol^-1 revealed no biocidal potential. Therefore, hydrolysable polycations were prepared, which show a broad band activity against different Gram-positive and Gram-negative strains. After hydrolyzation these polymers lose their biocidal activity and the most important part is the degradation rate of these polymers. At standard lab conditions at pH 10 these polymers are deactivated after 120 minutes and even after 30 minutes they reach the same niveau that the poly(2-oxazolines) reached in total. More important this degradation is also working at pH 7, which means that not even enzymes have to catalyze the degradation of the polymers to nonactive and non-toxic oligomers. In the best case this complete deactivation of the polymer is performed at pH 7 after 4 days.
Publications
- Conjugation of Ciprofloxacin with Poly(2-oxazoline)s and Polyethylene Glycol via End Groups, Bioconjugate Chemistry 26 (9), 1950-1962 (2015)
M. Schmidt, S. Harmuth, B. E. Barth, E. Wurm, R. Fobbe, A. Sickmann, C. Krumm, J. C. Tiller
(See online at https://doi.org/10.1021/acs.bioconjchem.5b00393) - Chapter 15 Antimicrobial Polymers and Surfaces - Natural Mimics or Surpassing Nature?, Bio-inspired Polymers, The Royal Society of Chemistry, 490-522 (2017)
C. Krumm, J. C. Tiller
(See online at https://doi.org/10.1039/9781782626664-00490) - Highly active and selective telechelic antimicrobial poly(2-oxazoline) copolymers, Polymer 118, 107-115 (2017)
C. Krumm, H. Montasser, S. Trump, S. Saal, L. Richter, G. G. F. K. Noschmann, T.-D. Nguyen, K. Preslikoska, T. Moll, J. C. Tiller
(See online at https://doi.org/10.1016/j.polymer.2017.04.074) - Poly(2-oxazoline)-Antibiotic Conjugates with Penicillins, Bioconjugate Chemistry 28 (9), 2440-2451 (2017)
M. Schmidt, L. K. Bast, F. Lanfer, L. Richter, E. Hennes. R. Seymen, C. Krumm, J. C. Tiller
(See online at https://doi.org/10.1021/acs.bioconjchem.7b00424) - Telechelic, Antimicrobial Hydrophilic Polycations with Two Modes of Action, Macromolecular Bioscience 18 (4), 1700389 (2018)
L. Richter, M. Hijazi, F. Arfeen, C. Krumm, J.C. Tiller
(See online at https://doi.org/10.1002/mabi.201700389)
