Printing a cure: A tailored solution for localized drug delivery in liver cancer treatment

Int J Pharm. 2024 Feb 15:651:123790. doi: 10.1016/j.ijpharm.2024.123790. Epub 2024 Jan 6.

Abstract

Adjuvant chemotherapy is highly recommended for liver cancer to enhance survival rates due to its tendency to recur frequently. Localized drug-eluting implants have gained traction as an alternative to overcome the limitations of systemic chemotherapy. This work describes the development of biodegradable 3D printed (3DP) bilayer films loaded with 5-fluorouracil (5FU) and cisplatin (Cis) with different infill percentages where the 5FU layers were 40%, 30%, and 30% and Cis layers were 10%, 15%, and 10% for films A, B, and C, respectively. The relevant characterization tests were performed, and the drug content of films was 0.68, 0.50, and 0.50 mg of 5FU and 0.39, 0.80, and 0.34 mg of Cis for films A, B, and C, respectively. Cis release was affected by the alterations to the film design, where films A, B, and C showed complete release at 12, 14, and 23 days, respectively. However, 5FU was released over 24 h for all films. The films were stable for up to two weeks after storage at 25 °C/65% relative humidity and four weeks at 4 °C where drug content, tensile strength, FTIR, and thermal analysis results demonstrated negligible alterations. The cytotoxicity of the films was assessed by MTS assays using HepG2 cell lines demonstrating up to 81% reduction in cell viability compared to blank films. Moreover, apoptosis was confirmed by Western Blots and the determination of mitochondrial cell potential, highlighting the potential of these films as a promising approach in adjuvant chemotherapy.

Keywords: 3D printing; 5 Fluorouracil; Cisplatin; Liver cancer; Personalized medicine.

MeSH terms

  • Apoptosis
  • Cisplatin
  • Drug Delivery Systems* / methods
  • Fluorouracil
  • Humans
  • Liver Neoplasms* / drug therapy
  • Printing, Three-Dimensional

Substances

  • Fluorouracil
  • Cisplatin