Prevention of implant associated infection by smart drug delivery

(Y. Bourgat, C. Mikolai, P. Klahn, B. Tiersch and H. Menzel)

Enzyme degradable polymersomes from Chitosan‑g‑[Poly‑L‑Lysine‑Poly-ε-Caprolacton] copolymer

The long-term development and success of dental implants depends largely on the ability to keep them free of infections and with that to avoid any further surgical treatments. This research is designed to provide a pharmaceutical solution that prevents implant-associated infections. To face this challenge, a new amphiphilic graft-copolymer based on two biocompatible polymers, chitosan (CS) and polycaprolactone (PCL) is introduced and studied. The graft-copolymer can self-assemble into polymeric micelles via solvent shift method with a well-defined core-shell structure suitable for encapsulation. The hydrophobic (PCL) and the hydrophilic (CS) parts are linked via a biocompatible enzyme cleavable peptide. The polymersomes, as well as a coated layer on titanium, result in a highly stable system at body temperature, which is an essential requirement for a drug delivery system. Furthermore, degradability is studied by incubating polymersomes with two enzymes, peptidase, and chitosanase. Indeed, specific peptidases that are released as a result of an inflammation could be used to trigger drug releases. The synthetic route involves the functionalization of CS with maleimide groups^[1] and PCL with an alkyne end-group^[2]. Thiol-en click-chemistry and azide-alkyne Huisgen-cycloaddition are used to link chitosan and poly-caprolactone chains, respectively, via the peptide linker. Therefore, a thiol and azide functionalized peptide were used to generate this system.

Enzyme-responsive nanoparticles (NP) made from alginate/peptide ciprofloxacin avoiding burst releases

In recent years, hydrogel nanoparticles have gained public interest and have become one of the most promising drug delivery systems. The main advantage is that they can be tuned to generate stimuli-responsive systems. Stimuli such as pH, temperature, redox, electricity, and magnetic fields are commonly used^[3]. The liberation of specific enzymes can also trigger the drug release and generate a highly specific on‑demand delivery system.^[4] This kind of triggered release could be particularly beneficial in preventing implant-associated infections (IAI) and the overuse of antibiotics.^[5] In response to these challenges, new alginate/peptide nanoparticles have been prepared. The system integrates a peptide designed to build a covalent link with active substances. Ciprofloxacin was used in this study as a model substance. The positively charged peptide conjugated drug was able to self-assemble into nanoparticles via ionic gelation with a negatively charged alginate. The peptide sequence is also uniquely able to be cleaved by specific enzymes. This peptide cleavage leads to the disruption of the hydrogel network, which causes a controlled release without the burst effect. The nanoparticles, as well as a coated layer on the titanium, result in a highly stable system at body temperature.