Development of a γ-Cyclodextrin-Based Cryogel Loaded with Trimethoprim for Acne Treatment: Design, Synthesis, and In Vitro Evaluation

Innovative functional materials integrating host-guest complexes in cryogels offer promising applications in topical drug delivery, enhancing drug solubility and stability. In this study, we designed and developed a cryogel-based patch for acne treatment by polymerizing an acrylate-functionalized gamma-cyclodextrin (gamma-CD) and trimethoprim (TMP) inclusion complex with [2-(acryloyloxy)ethyl]trimethylammonium chloride (AETMA) at low temperatures. A multistep workflow was applied to synthesize the inclusion complex via mortar-assisted kneading, followed by cryogel formulation through radical cryopolymerization. The resulting hybrid system leverages the cationic nature of AETMA to promote adhesion and electrostatic interactions with the skin surface. At the same time, gamma-CD serves as a drug reservoir, facilitating sustained release of the drug. The system was characterized by FT-IR, TGA, and SEM analyses. In vitro release studies demonstrated a sustained TMP release profile, best described by the Korsmeyer-Peppas diffusion model. Antibacterial assays confirmed the system's effectiveness against Staphylococcus aureus, supporting its potential for localized and prolonged acne treatment. Moreover, cytocompatibility tests demonstrated that the formulation is biocompatible, further validating its suitability for topical application.