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Nanoreactors for local production and release of antibiotic

Langowska, Karolina. Nanoreactors for local production and release of antibiotic. 2013, PhD Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_10361

Abstract

Implant infections are emerging as a grave medical problem.The number of medical and surgical procedures involving medical implant devices will continue to grow, for example due to aging of the population. Device-associated infections are a consequence of bacterial adhesion and subsequent biofilm formation at the implantation site. Due to the importance of this problem, intense research is being focused on finding new, efficient treatments. Conventional antibiotic therapies remain ineffective and very often lead to removal of the contaminated device. Various alternative strategies have been proposed, however, these suffer from many drawbacks. Tackling infections associated with medical implants remain a challenge.
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)
Item Type:Thesis
Thesis no:10361
Bibsysno:Link to catalogue
Number of Pages:93 S.
Language:English
Identification Number:
Last Modified:30 Jun 2016 10:52
Deposited On:06 May 2013 14:11

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