In-chain poly(phosphonate)s : synthesis, degradation and biomedical applications
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Abstract
Application of polymers as biomaterials has greatly impacted the progress of modern medicine. Especially degradable polymers are of particular interest for biomedical applications because they can be eliminated from the body after fulfilling their task. For biomaterials, a precise adjustment of their chemical and physical properties as well as their degradation behavior is crucial to adapt them to the respective requirements.
Poly(phosphoester)s (PPEs) are particularly relevant for the application as biomaterials due to their potential biodegradability and biocompatibility. In addition, the pentavalency of phosphorus offers a variety of possibilities for precise adjustment of desired properties: The nature of the organic spacers in the polymer backbone allows a variation of the polarity and is crucial for the crystallization behavior of PPEs, while the binding motif around the central phosphorus atom is crucial to influence their degradation profile. In addition, the side chain can be used to introduce functional groups.
In the course of this work, diverse monomers were developed that facilitated and simplified the synthesis of PPEs with variable properties in terms of solubility, degradation behavior and stability through targeted structural changes.
Furthermore, PPEs with different binding motifs were investigated for their recently discovered "stealth" properties. Therefore, PPE-based surfactants were synthesized and applied for the surface modification of nanoparticles consisting of different materials. The modified particles were evaluated with regard to their blood circulation times. In the next step, PPE-surfactants were additionally modified with mannose-units, which allowed a targeted addressing of cells of the immune system. It was shown that the surface modification of nanoparticles with PPE surfactants is suitable for prolongation of the blood circulation times and for the targeted addressing of specific cells while it required low synthetic effort. Finally, PPEs with different binding motifs were evaluated with regard to their degradability under basic conditions. It was shown that even small structural variations led to significantly altered degradation profiles.