Bacteria-responsive materials for drug delivery

The number of diabetics, obese individuals and other patients carrying other lifestyle diseasesis increasing worldwide. At the same time the population is ageing. These patients all sufferfrom poor blood circulation, which often gives rise to non-healing, or chronic, wounds. Thus,the number of chronic wounds is also increasing at a fast pace. Such wounds often carryinfection since the wound environment is favorable for bacteria. The wounds cause pain, odorand can lead to amputation or even death. Hence, the patients are treated with systemic andtopical antimicrobial substances, e.g. antibiotics. However, the overexposure and misuse ofsuch drugs has created another issue worldwide: bacterial resistance. There are already someinfections that are difficult to treat due to the rapid development of bacterial resistance andfewer working drugs.Our work has focused on a release platform that can administer drugs only when a woundshows signs of infection. By sensing the type of infection at hand, the release system shouldbreak down and expose a suitable antimicrobial substance to the bacteria. Such a releasesystem would not only combat the infection but also decrease the risk of bacterial resistanceand other side effects on the patient, since it would be administered locally and only when it isneeded.Two bacteria were chosen as targets, Staphylococcus aureus and Pseudomonas aeruginosa,which often are pathogenic in chronic wounds. Both bacteria exude very substrate specificproteases, i.e. V8 and Protease IV, respectively. Hence, nanofilms corresponding to eachprotease were assembled via the layer-by-layer route. V8 readily degrades peptide bondsinvolving poly-L-glutamic acid (PLGA), which also was the main component in the releasesystem against S. aureus, while Protease IV degrades bonds involving poly-L-lysine, whichhence was used as component in the release system against P. aeruginosa. The nanofilmswere found not to be degraded by normal human enzymes; however, each bacterial proteaseruptured their respective film if they reached a concentration similar to the concentrationfound in a chronic wound. Consequently, the drug was released or exposed only when incontact with the bacterial enzymes. Such release systems could be used to fight infectionwhile avoiding bacterial resistance and misuse of antimicrobials