Determining loading kinetics of drug releasing degradable shape-memory polymers
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Determining loading kinetics of drug releasing degradable shape-memory polymers Christian Wischke1, Susi Steuer2, and Andreas Lendlein1 1
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Center for Biomaterial Development and Berlin-Brandenburg Center for Regenerative Therapies, Institute for Polymer Research, Helmholtz-Zentrum Geesthacht, Kantstr. 55, 14513 Teltow, Germany present address: Intervet Innovation GmbH, 55270 Schwabenheim, Germany
ABSTRACT Modern concepts for biofunctional implants often comprise the controlled release of bioactive compounds to gain specific biofunctionalities. Here, amorphous and semi-crystalline copolyester-based shape-memory polymer (SMP) networks are reported as matrix for pharmaceutical applications. Drug loading of such crosslinked networks by swelling techniques requires tools to determine the actual payload. In this report, the capability of determining loading kinetics by mass increase or changes of drug concentration in the swelling medium is explored for two types of copolyester-based SMP networks differing in their crosslinking chemistry. Nitrofurantoin and ethacridine lactate served as hydrophobic and hydrophilic model drugs. It was found, that the absolute values of the determined payload did not systematically agree with those obtained by the more reliable technique of network cleavage and spectrophotometric quantification. However, the studies indicate that for both types of SMP materials and both drugs, maximum incorporation of the drugs occurred within a few hours. The time until equilibration depended on the network properties. INTRODUCTION The application of polymer-based biomaterials as implants sets high requirements for the employed matrices. Typically, implants are supposed to fulfill specific tasks after implantation, such as providing structural support, bridging lesion sites, or providing bioactive substances to induce a demanded pharmacological effect. In addition to the type and content of its building blocks, polymer design strongly involves the setup of defined architectures and morphologies. These tools enable to create materials, which can fulfill the demands set by the trend towards more sophisticated medical applications of polymeric implants [1]. One of these requirements is the capability of implants to provide a well-defined mechanical actuation in vivo, which could for instance be used to anchor implants in the tissue upon application of a suitable stimulus. Shape memory-polymers (SMPs) are active polymers, which can perform changes of their shape in a predefined manner. This functionality bases on polymer networks with permanent netpoints, which are connected by flexible polymer segments (switching segments). In temperature-sensitive SMPs, these switching segments can be fixed by cooling below the thermal transition temperature of the associated domains, which can correspond to a melting transition or a glass transition. Recently, covalently crosslinked shape-memory polymers were reported to combine additional functionalities, namely degradability and drug release. Such materials can be obt
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