Novel degradablepolymeric materials for biomedical and antibacterial applications

In dieser Arbeit wurden abbaubare Polymere für drei verschiedene Anwendungen designt, synthetisiert und charakterisiert: DNA-Transfektion, Wirkstofffreisetzungen und antibakterielle Materialien. Im ersten Teil der DNA-Transfektion wurden das neuartige abbaubare und biokompatible Poly(PEG-co-(BMDO-...

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Bibliographische Detailangaben
1. Verfasser: Zhang, Yi
Beteiligte: Agarwal, Seema (Prof. Dr.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Veröffentlicht: Philipps-Universität Marburg 2012
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Inhaltsangabe: In this thesis degradable polymers for three different purposes, DNA transfection, drug delivery and antibacterial properties were designed, synthesized and characterized. In the first part of the DNA transfection application the novel degradable and biocompatible poly(PEG-co-(BMDO-co-DMAEMA)) and its quaternized derivative poly(PEG-co-(BMDO-co-DMAEMA•EtBr)) were successfully synthesized and characterized. This copolymer shows a significant solubility improvement by introducing hydrophilic PEG blocks into the polymer backbone. The successful incorporation of ester linkages into the copolymer backbone led to a fast degradation of the copolymer under enzymatic and buffer conditions. All the synthesized copolymers show a low cytotoxicity. The unquaternized copolymers result in higher cell viability than the quaternized copolymers as well as positive results in p-DNA transfection. In the second part of the DNA transfection application degradable and biocompatible poly(PEG-co-(MDO-co-DMAEMA)) and the quaternized derivative poly(PEG-co-(MDO-co-DMAEMA•EtBr)) were obtained also via free radical polymerization using PEG macro azo initiator. The presence of the PEG unit in the polymer backbone led to great improvement of the polymer solubility. The more reactive MDO leads to a higher ester content in the copolymer than with BMDO as monomer. After quaternization of poly(PEG-co-(MDO-co-DMAEMA), the solubility of the polymers as well as their complexation efficiencies were greatly improved. This highly biocompatible polymer shows a positive result in the gene transfection experiments in the presence of serum. For the drug delivery application, a biocompatible and degradable functional polymer which is based on HEMA could be successfully synthesized by radical polymerization. The structure of the resulting polymers and the reaction kinetics was studied in this work. The cell viabilities were over 80 % even for very high polymer concentrations (100 mg/ml). The hydroxyl functionalized polymers are hydrolytically degradable under basic conditions and also show surface erosion and bulk degradation upon treatment with macrophages. A promising positive result is demonstrated for the use of such polymers for drug encapsulation. This new, well characterized biocompatible and degradable hydroxyl functionalized polymer could be suitable for many different biomedical applications. For the antibacterial application, poly(BMDO-co-HEMA-graft-DMAEMA) with different DMAEMA side chain lengths was synthesized using a new macro ATRP initiator. A high water absorption ability of these copolymers can be observed. At higher temperature and lower pH the polymer with 43 wt.% of DMAEMA shows the highest water uptake efficiency. Poly(BMDO-co-HEMA-graft-DMAEMA) demonstrates great antibacterial activities against both E. coli and Bacillus Subtilis down to concentrations as low as 31.25 µg/mL. The time dependent antibacterial test shows that 99.9 % of the treated E. coli bacteria were killed within 1 minute. This polymer also presents slow degradation ability under compost condition.