Curcumin Imprinted Supermacroporous Poly(Hydroxyethyl Methacrylate) Based Cryogels for Effective Controlled Drug Release

This study aimed to develop curcumin-imprinted poly(HEMA-MAH-Cu²⁺) cryogel discs as a controlled and stimuli-responsive drug delivery system, addressing the poor solubility and limited bioavailability of curcumin through molecular imprinting and metal-ion-mediated complexation. Cryogels were synthesized via cryopolymerization using various monomer and crosslinker ratios and different drug loadings. N-methacryloyl-(L)-histidine methyl ester (MAH) served as the functional monomer, forming a Cu²⁺-mediated metal-chelation complex with curcumin prior to polymerization. Structural characterization of curcumin-imprinted cryogels was conducted using FTIR, SEM, BET, DSC, XRD, and Micro-CT analyses. In vitro curcumin release studies were conducted under different pH and temperature conditions, and release kinetics were evaluated using the Korsmeyer–Peppas model. Cytotoxicity and biological performance were assessed using L929 fibroblast cells, MDA-MB-231 breast cancer cells, and antibacterial disk diffusion assays. Structural analyses confirmed the formation of an interconnected macroporous cryogel network with tunable pore size, surface area, and swelling behavior. In vitro release studies demonstrated that curcumin release was strongly dependent on polymer composition and environmental conditions, with a maximum cumulative release of approximately 60% achieved under physiological conditions (pH 7.4, 37 °C). Release kinetics followed a non-Fickian diffusion mechanism. Cytocompatibility tests showed that curcumin-imprinted cryogels maintained >98% cell viability in L929 fibroblast cells, indicating good biocompatibility. In contrast, curcumin-loaded MIP cryogels reduced the viability of MDA-MB-231 breast cancer cells by approximately 75–80% after 48 h. Additionally, curcumin-loaded cryogels exhibited clear antibacterial activity against both Gram-positive and Gram-negative bacteria. Curcumin-imprinted poly(HEMA-MAH-Cu²⁺) cryogels demonstrated favorable structural, release, cytotoxicity, and antibacterial characteristics, highlighting their strong potential for controlled and targeted drug delivery applications.