3D printed intrauterine device development containing dual anticancer drugs for the treatment of uterine cancer
Uterine cancer is a major global health problem and treatment frequently includes invasive surgery that severely compromises fertility. Current systemic chemotherapeutic drugs, such as paclitaxel (PCX) and carboplatin (CBP), lack an established standard protocol and their efficacy is limited. This study focuses on the development of a personalized, local drug delivery system for the treatment of uterine cancer. The intrauterine devices (IUDs) were prepared using polycaprolactone (PCL) filaments containing PCX and CBP complexed to cyclodextrin (CD) to enhance the stability and solubility of the drugs during the printing process. The fused filament fabrication (FFF) type 3D printing technique, owing to its precise computer-aided layer deposition, successfully provided a platform for geometric and dosage personalization, achieving high dimensional accuracy. Physicochemical characterization studies showed that CD inclusion complexes maintained drug stability during the printing process, confirmed by the absence of free crystalline drug. Furthermore, drug:CD complexes significantly enhanced the mechanical properties of PCL, thereby increasing strength and toughness, which are critical for intrauterine stability. In vitro release studies demonstrated a sustained, controlled release profile, exceeding 80% over 9 months for PCX and 4 months for CBP. Cytotoxicity studies showed that drug-free IUDs were non-cytotoxic and non-genotoxic to healthy L929 mouse fibroblast cells. Furthermore, in vivo studies demonstrated that IUDs did not cause dermal irritation. The drug-containing IUDs were found to be at least as effective as the drug solution on HEC-1B endometrial cancer cells. Lastly, ex vivo studies confirmed favorable bioadhesion of IUDs and high drug retention within uterine tissue. All these findings validate the FFF-type 3D printing as a promising and flexible approach for preparing personalized, biocompatible, and effective local drug delivery systems for the treatment of uterine cancer.