Photo-crosslinked biodegradable polymer networks for controlled intraocular drug delivery

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In this thesis the potential of photo-crosslinked polymer networks for intraocular drug delivery is described. Patients with diseases of the back of the eye would benefit considerably from the development of drug delivery systems that can provide sustained intraocular delivery for months to years. Due to their versatility, photo-crosslinked polymer networks are an interesting class of materials for application in drug delivery systems. Photo-crosslinked polymer networks are often prepared from oligomers that are end-functionalized with double bond-containing groups. Many of the networks described in this thesis were prepared from oligomers functionalized with fumaric acid monoethyl ester (FAME). The possibilities of preparing photo-crosslinked polymer networks using these end-groups were explored. The work described in this thesis demonstrates that photocrosslinked polymer networks with diverse properties can be prepared from FAMEfunctionalized oligomers. By varying factors such as the crosslink density and network hydrophilicity, release profiles could be tuned. Model proteins could be released in a controlled way over periods of a few months. Therefore the prepared networks hold promise for the intraocular delivery of protein drugs. Importantly, an initial in vivo study indicated that photo-crosslinked polymer networks are well tolerated in the rabbit vitreous. However, there also remain challenges that need to be solved. Due to their large size and relative instability the controlled release of proteins remains challenging. Side reactions may occur during the network formation process and interactions of the protein with the polymer matrix may lead to incomplete protein release. It was shown that side reactions can be minimized if the network preparation process is optimized carefully, but these issues need further attention in the future. In vivo release studies with one of the networks that displayed attractive release profiles could be a next step towards an intraocular drug delivery system based on photocrosslinked polymer networks.