Bacteria-responsive materials for drug delivery
Doktorsavhandling, 2015

The number of diabetics, obese individuals and other patients carrying other lifestyle diseases is increasing worldwide. At the same time the population is ageing. These patients all suffer from 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 carry infection since the wound environment is favorable for bacteria. The wounds cause pain, odor and can lead to amputation or even death. Hence, the patients are treated with systemic and topical antimicrobial substances, e.g. antibiotics. However, the overexposure and misuse of such drugs has created another issue worldwide: bacterial resistance. There are already some infections that are difficult to treat due to the rapid development of bacterial resistance and fewer working drugs. Our work has focused on a release platform that can administer drugs only when a wound shows signs of infection. By sensing the type of infection at hand, the release system should break down and expose a suitable antimicrobial substance to the bacteria. Such a release system would not only combat the infection but also decrease the risk of bacterial resistance and other side effects on the patient, since it would be administered locally and only when it is needed. Two bacteria were chosen as targets, Staphylococcus aureus and Pseudomonas aeruginosa, which often are pathogenic in chronic wounds. Both bacteria exude very substrate specific proteases, i.e. V8 and Protease IV, respectively. Hence, nanofilms corresponding to each protease were assembled via the layer-by-layer route. V8 readily degrades peptide bonds involving poly-L-glutamic acid (PLGA), which also was the main component in the release system against S. aureus, while Protease IV degrades bonds involving poly-L-lysine, which hence was used as component in the release system against P. aeruginosa. The nanofilms were found not to be degraded by normal human enzymes; however, each bacterial protease ruptured their respective film if they reached a concentration similar to the concentration found in a chronic wound. Consequently, the drug was released or exposed only when in contact with the bacterial enzymes. Such release systems could be used to fight infection while avoiding bacterial resistance and misuse of antimicrobials.

multilayer

enzymatic degradation

controlled release

triggered release

infection

Layer-by-layer

nanofilm

sal KA
Opponent: Gerald Brezesinski

Författare

Marina Craig

Chalmers, Kemi och kemiteknik, Tillämpad kemi, Teknisk ytkemi

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I vårt arbete har vi fokuserat på två bakterier som ofta skapar infektion i sår, Staphylococcus aureus samt Pseudomonas aeruginosa. Dessa två är inte alltid patogena (skapar sjukdom), men ändå utgör de det största hotet för patienter med sår, speciellt för dem med kroniska sår. Att denna patientgrupp växer lavinartat hör samman med ökat antal välfärdssjukdomar (t.ex. diabetes och fetma), samt med ett ökat antal äldre personer (blodcirkulationsrelaterade åkommor). Grundidén till projektet ligger i att bygga en tunn film (ej synlig för blotta ögat) som kan brytas ner med hjälp av en specifik bakterie. Genom att bygga sådana filmer på en yta eller som skalet på en kapsel, kan bakteriedödande substanser inkorporeras antingen i filmen eller i kapselns inre. Då de tunna filmerna är byggda med S. aureus eller P. aeruginosa i åtanke, skall filmen brytas ner i kontakt med den bakterie den är avsedd för och på så sätt också exponera den bakteriedödande substansen. Med andra ord skulle man endast utsätta såret för behandling om en infektion är närvarande och på så sätt minska användandet av antibiotika. Detta skulle kunna leda till färre resistenta bakterier, mindre lidande för patienten, lägre behandlingskostnader och en möjlighet att rikta behandlingen beroende på vilken organism som skapat infektionen. Vi har skapat två olika filmer, en för vardera bakterie (nämnda ovan), som bryts ner i närvaro av infektion.

In our work we have focused on two bacteria that cause infection in wounds, Staphylococcus aureus and Pseudomonas aeruginosa. These bacteria are not always pathogenic (create disease), but they are still a major threat for patients with wounds, particularly if the wounds are chronic. The number of patients with chronic wounds is growing fast due to an increase in lifestyle diseases (e.g. diabetes and obesity) and a larger ageing population (poor blood circulation). The idea of the work is based on assembling thin films (not visible for the naked eye) that can be degraded by specific bacteria. The films can be assembled on a surface or as a shell on a capsule with an antimicrobial drug inside the film or inside the capsule. Since the films are built with S. aureus and P. aeruginosa in mind, the film should be degraded when exposed to the bacterium it was meant for, and thus also exposing the antimicrobial drug. In other words, such a system would only release the drug if an infection was present, which in the end would decrease unnecessary drug exposure. This could lead to less resistant bacteria, less suffering for the patient, lower treatment costs and a possibility to target the treatment depending on the type of infection. We have created two different films, one for each bacterium named previously in the text, which are degraded when in contact with infection.

Ämneskategorier

Materialkemi

Styrkeområden

Materialvetenskap

ISBN

978-91-7597-243-5

sal KA

Opponent: Gerald Brezesinski

Mer information

Skapat

2017-10-07