Browsing by Author "Korhonen, Harri, Dr., Aalto University, Finland"

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Crosslinked poly(ester anhydrides) for controlled drug delivery
(2013) Hakala, Risto
School of Chemical Technology | Doctoral dissertation (article-based)
Bioresorbable polymers are extensively studied materials for medical applications. In this work, novel bioresorbable polymers, hydrophobically-modified crosslinked poly(ester anhydride) networks, were developed and characterized with the aim of obtaining suitable matrices for controlled drug release applications. In these free-radically crosslinked poly(ester anhydride) networks were combined the favorable characteristics of synthetic aliphatic polyesters and polyanhydrides. The properties of the poly(ester anhydride) networks were altered by modifying the structure of the poly(epsilon-caprolactone) oligomers which were used in the preparation of the crosslinkable poly(ester anhydride) precursors. The molecular weight and architecture of the poly(epsilon-caprolactone) oligomers were controlled by using different types and amounts of co-initiator in the ring-opening polymerization. The hydrophobicity of the oligomers was modified by end-functionalizing the hydroxyl-telechelic oligomers with different alkenylsuccinic anhydrides. Crosslinkable precursors with reactive double and labile anhydride bonds were obtained by methacrylating the acid-terminated oligomers with methacrylic anhydride. Finally, the poly(ester anhydride) precursors were crosslinked to networks either thermally or by using visible light. The change in the molecular architecture of the precursor from linear to star-shaped increased crosslinking density and raised the gel contents. In the hydrolysis studies the more hydrophobic samples, i.e., networks containing alkenyl chains, eroded slower than the networks without the alkenyl chains. In addition, some of the crosslinked samples exhibited clear signs of surface erosion: a linear mass loss but practically intact core. Increase in the molecular weight and hydrophobicity of the precursor changed the erosion mechanism of the networks from surface toward bulk erosion. The mild photocrosslinking conditions of these poly(ester anhydride) networks enable the incorporation of sensitive active agents, such as peptide- and protein-based drugs, with reduced risk of inactivation. The photocrosslinked networks provided sustained and surface erosion controlled in vivo release of model peptide YY3-36. Furthermore, the in vivo release could be tailored by modifying the hydrophobicity of the network. These novel polymeric drug delivery materials exhibit high potential for applications requiring controlled release of sensitive macromolecular pharmaceutical agents.