Thermally on-off switching polymers for drug permeation and release

The swelling of crosslinked poly(N,N'-alkyl substituted acrylamides) in water was studied in relation to changes in external temperature. The significant swelling changes of the polymer in water in response to temperature can be attributed to the delicate hydrophilic/hydrophobic balance of the polymer chain, and was affected by the size, configuration and mobility of the alkyl side chains on the substituted acrylamides. Sharp swelling transitions may occur at an optimum hydrophilic/hydrophobic balance and was found only in N-isopropylacrylamide network, among the tested networks. Copolymers including crosslinked poly(N-isopropylacrylamide (IPAAm)-co-butylmethacrylate (BMA)) and interpenetrating polymer networks (IPNs) of poly(IPAAm) and poly tetramethylene ether glycol (PTMEG) were also synthesized and investigated as modified IPAAm networks. The gel shrinking behavior for a disk-shaped geometry (10 mm diameter, 0.7 mm thickness) with increasing temperature was affected by the gel composition and fabrication techniques. An important observation in these studies was that the initial shrinkage of the gel occurred on the surface of the membrane. The consequence of this phenomenon was that the outer surface (skin) formed a denser structure, as compared to the bulk of the membrane, which regulated water and subsequently solute transport. To evaluate the controlled release aspects of these “thermosensitive” networks, indomethacin (a model drug) was solution loaded into the devices. The release of indomethacin from the gels correlated with the observed swelling properties. At low temperature, indomethacin followed pseudo-zero-order or first-order release kinetics, depending on the matrices, while at elevated temperatures indomethacin failed to diffuse out of the gels. This “on-off ” release in response to temperature was restricted to a narrow temperature range. The lag time and release profile in the low temperature region of each temperature cycle was influenced by the composition of the copolymer or IPNs. In addition, the permeation of insulin and glucose through the same membrane demonstrated a similar on-off mechanism in response to temperature.

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