Abstract
Background:
Liver cancer is characterized by a high recurrence rate, making adjuvant chemotherapy essential for improving survival outcomes. However, conventional systemic chemotherapy is associated with limited targeting efficiency and increased systemic toxicity. Localized drug delivery systems, such as drug-eluting implants, offer a promising strategy to overcome these limitations.

Purpose:
This study aimed to develop biodegradable 3D-printed (3DP) bilayer films loaded with 5-fluorouracil (5FU) and cisplatin (Cis) as a tailored solution for localized drug delivery in liver cancer treatment.

Materials and Methods:
Bilayer films (A, B, and C) were fabricated using 3D printing with varying infill percentages—5FU layers (40%, 30%, and 30%) and Cis layers (10%, 15%, and 10%), respectively. The films were evaluated for drug content, release kinetics, mechanical properties, and stability under different storage conditions. Characterization techniques included FTIR and thermal analysis. Cytotoxicity was assessed using MTS assays on HepG2 liver cancer cell lines, while apoptosis was evaluated through Western blot analysis and mitochondrial membrane potential studies.

Results:
The drug content of the films ranged from 0.50 to 0.68 mg for 5FU and 0.34 to 0.80 mg for Cis across different formulations. Cisplatin release was influenced by film design, with complete release observed at 12, 14, and 23 days for films A, B, and C, respectively. In contrast, 5FU exhibited rapid release within 24 hours in all formulations. Stability studies demonstrated that the films remained stable for up to two weeks at 25 °C/65% relative humidity and four weeks at 4 °C, with negligible changes in drug content, tensile strength, FTIR spectra, and thermal properties. Cytotoxicity studies revealed up to 81% reduction in HepG2 cell viability compared to blank films. Apoptotic activity was confirmed through Western blot analysis and mitochondrial membrane potential disruption.

Conclusions:
The developed biodegradable 3D-printed bilayer films demonstrate significant potential as a localized drug delivery system for liver cancer treatment. The combination of rapid 5FU release and controlled cisplatin release, along with strong anticancer activity, supports their application as an effective strategy for adjuvant chemotherapy.