Langowska, Karolina. Nanoreactors for local production and release of antibiotic. 2013, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_10361
In this thesis, enzymatically active, covalently immobilized nanoreactors based on poly(2-methyloxazoline)-block-poly(dimethylsiloxane)-block-poly(2-methyloxazoline) (PMOXA-b-PDMS-b-PMOXA) amphiphilic block copolymer were designed and prepared. These nanoreactors catalyzed the conversion of prodrug molecules, which exhibit no antibacterial activity, to a drug active as an antibiotic. The enzymatic conversion was shown to occur only inside the nanoreactors. When these are immobilized they represent a novel, nanosized system whereby a drug will not be released to the entire body, but will be synthesized in situ. This strategy offers multiple advantages: long term production of antibacterial compounds due to the protection of the enzyme from proteolytic degradation, control of drug production at a specific rate for a specific period of time, and localized drug delivery.
First, cationic ring opening polymerization was employed to synthesize the polymer. The self-assembly of this polymer was studied, as was the enzymatic activity of the resulting nanoreactor. The covalent attachment of the nanoreactors to a surface was realized by two different strategies: (i) attachment via an amino bond, involving Schiff base formation and its further reduction (ii) attachment via photo-cleavage by a phenyl azido linker. Both approaches resulted in successful, stable immobilization. The attached nanoreactors were characterized by surface-sensitive techniques such as scanning electron microscopy and atomic force microscopy. Experiments with bacteria were conducted to demonstrate the antimicrobial potential of surface immobilized enzymatically active nanoreactors.
In summary, this thesis develops the concept of polymeric nanoreactors that synthesize drugs in situ to inhibit bacterial growth. Additionally, the immobilization methodologies elaborated within the scope of this work could be further adapted for potential applications in biotechnology and biosensing.
|Advisors:||Meier, Wolfgang Peter|
|Committee Members:||Textor, Marcus|
|Faculties and Departments:||05 Faculty of Science > Departement Chemie > Chemie > Makromolekulare Chemie (Meier)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||93 S.|
|Last Modified:||30 Jun 2016 10:52|
|Deposited On:||06 May 2013 14:11|
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