Design of thermoresponsive hydrogels by controlling the chemistry and imprinting of drug molecules within the hydrogel for enhanced loading and smart delivery of drugs

Various drug delivery techniques have contributed significantly to medical practice. In particular, molecular imprinting is a suitable method to increase the drug-loading efficiency in limited 3D spaces, such as hydrogels. This method has recently been studied for the transdermal delivery of various therapeutic agents, but its full potential is yet to be achieved in molecular systems. In this study, thermoresponsive and molecularly imprinted hydrogels were prepared by radical polymerization with molecular imprinting using three types of drug molecules as templates. The drug templates—acyclovir (ACV), diclofenac (DFN), and doxorubicin (DXR)—were used to establish molecular correlations between molecularly imprinted hydrogels and drug molecules by using non-covalent lewis acid-base interactions, hydrophilicity and molecular size. The DXR-imprinted hydrogel exhibited a much greater imprinting efficiency than ACV- and DFN-imprinted hydrogels because of the hydrophilic characteristics and large molecular size of DXR compared with the other drugs. The morphology, surface area, and swelling behavior, dependent on the temperature, were also investigated. The in vitro drug release studies performed at various temperatures revealed the unique drug release profiles unlike previous thermoresponsive studies. This study demonstrated a facile strategy to construct molecularly imprinted hydrogels that have the thermoresponsive delivery, and offer new guidelines to identify optimal combination between the drugs and hydrogels.