Enzyme Responsive Hyaluronic Acid Nanocapsules Containing Polyhexanide and Their Exposure to Bacteria To Prevent Infection

Abstract

Antibacterial nanodevices could bring coatings of plastic materials and wound dressings a big step forward if the release of the antibacterial agents could be triggered by the presence of the bacteria themselves. Here, we show that novel hyaluronic acid (HA)-based nanocapsules containing the antimicrobial agent polyhexanide are specifically cleaved in the presence of hyaluronidase, a factor of pathogenicity and invasion for bacteria like Staphylococcus aureus and Escherichia coli. This resulted in an efficient killing of the pathogenic bacteria by the antimicrobial agent. The formation of different polymeric nanocapsules was achieved through a polyaddition reaction in inverse miniemulsion. After the synthesis, the nanocapsules were transferred to an aqueous medium and investigated in terms of size, size distribution, functionality, and morphology using dynamic light scattering, zeta potential measurements and scanning electron microscopy. The enzyme triggered release of a model dye and the antimicrobial polyhexanide was monitored using fluorescence and UV spectroscopy. The stability of the nanocapsules in several biological media was tested and the interaction of nanocapsules with human serum protein was studied using isothermal titration calorimetry. The antibacterial effectiveness is demonstrated by determination of the antibacterial activity and determination of the minimal bactericidal concentration (MBC).

Enzyme-responsive nanocomposites for wound infection prophylaxis in burn management: in vitro evaluation of their compatibility with healing processes

“…However, exposure to enzymes that can be produced by common wound germs, eg, S. aureus will lead to the degradation and release of the antiseptic drugs. 13,14 In a comparative study of antiseptic efficacy, Koburger et al showed that for polyhexanide 0.5-2 mg/L and for octenidine 2 mg/L are required for a sufficient inhibition of S. aureus. 28 It should be highlighted that particularly at these concentrations the nanosystems have practically no negative influence on the cells even after 7-day exposure, in contrary to the agents alone.…”

“…13,14 However, for cell culture application, both samples were prepared using slightly modified procedures. Briefly, HYA-PHMB-NC were synthesized using the inverse mini-emulsion technique.…”

“…Fluorescent-labeled hyaluronan nanocapsules containing polyhexamethylene biguanide (HYA-PHMB-NC) 13 as well as poly-L-lactic acid nanoparticles loaded with octenidine (PLLA-OCT-NP) 14 have been previously described that display the above-named characteristics. Their susceptibility to degradation by hyaluronidase and proteinase facilitates a response to the most common germs found in infected burn wounds, such as Staphylococcus aureus and Pseudomonas aeruginosa.…”

Development and Characterization of Stimulus-Sensitive Nano/Microparticles for Medical Applications

“…This system can be modified to respond to other diseasespecific enzymes as well. Enzyme-responsive hyaluronic acid-based NPs were also developed to treat bacterial infection [46]. The NPs loaded with antimicrobial agent polyhexanide can be cleaved by hyaluronidase produced by several Gram-positive bacteria.…”

“…The NPs loaded with antimicrobial agent polyhexanide can be cleaved by hyaluronidase produced by several Gram-positive bacteria. The subsequent drug release would aid in killing bacteria effectively [46]. An example of chemical stimulus-responsive NPs is the DNA-functionalized gold NP aggregates linked using an adenosine aptamer.…”