Fused deposition modelling for the development of drug loaded cardiovascular prosthesis

Int J Pharm. 2021 Feb 15:595:120243. doi: 10.1016/j.ijpharm.2021.120243. Epub 2021 Jan 21.

Abstract

Cardiovascular diseases constitute a number of conditions which are the leading cause of death globally. To combat these diseases and improve the quality and duration of life, several cardiac implants have been developed, including stents, vascular grafts and valvular prostheses. The implantation of these vascular prosthesis has associated risks such as infection or blood clot formation. In order to overcome these limitations medicated vascular prosthesis have been previously used. The present paper describes a 3D printing method to develop medicated vascular prosthesis using fused deposition modelling (FDM) technology. For this purpose, rifampicin (RIF) was selected as a model molecule as it can be used to prevent vascular graft prosthesis infection. Thermoplastic polyurethane (TPU) and RIF were combined using hot melt extrusion (HME) to obtain filaments containing RIF concentrations ranging between 0 and 1% (w/w). These materials are capable of providing RIF release for periods ranging between 30 and 80 days. Moreover, TPU-based materials containing RIF were capable of inhibiting the growth of Staphylococcus aureus. This behaviour was observed even for TPU-based materials containing RIF concentrations of 0.1% (w/w). TPU containing 1% (w/w) of RIF showed antimicrobial properties even after 30 days of RIF release. Alternatively, these methods were used to prepare dipyridamole containing TPU filaments. Finally, using a dual extrusion 3D printer vascular grafts containing both drugs were prepared.

Keywords: 3D-printing; Dipyridamole; Fused deposition modelling; Rifampicin; Thermoplastic polyurethane; Vascular graft.

MeSH terms

  • Anti-Bacterial Agents / pharmacokinetics*
  • Blood Cells / drug effects
  • Blood Vessel Prosthesis / adverse effects
  • Delayed-Action Preparations / chemistry
  • Dipyridamole / pharmacokinetics
  • Drug Delivery Systems / methods*
  • Drug Liberation
  • Equipment Design / methods
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Polyurethanes / chemistry*
  • Polyurethanes / therapeutic use
  • Printing, Three-Dimensional
  • Rifampin / pharmacokinetics*
  • Staphylococcal Infections / etiology
  • Staphylococcal Infections / prevention & control
  • Staphylococcus aureus / drug effects
  • Technology, Pharmaceutical / methods*
  • Thrombosis / etiology
  • Thrombosis / prevention & control

Substances

  • Anti-Bacterial Agents
  • Delayed-Action Preparations
  • Platelet Aggregation Inhibitors
  • Polyurethanes
  • Dipyridamole
  • Rifampin