Fabrication of 5-fluorouracil-loaded tablets with hyperbranched polyester by digital light processing 3D printing technology

Abstract

Three-dimensional (3D) printing technique offers the possibility of producing personalized drug products. However, the suitable printing materials for vat photopolymerization in biomedical applications are still limited. In this study, the hydroxyl-terminated hyperbranched polyester (HBPE) was synthesized by 1,1,1-trimethylolpropane as a core moiety and 2,2-bis(hydroxymethyl)propionic acid as a branched monomer. HBPE was then reacted with acrylic acid (AA) to produce acrylated hyperbranched polyester (AHBPE). NMR analysis indicated that the degree of branching and number of hydroxyl group of HBPE were 0.40 and 19.5, respectively, while the degree of acrylation of AHBPE was 84.0%. AA as a monomer, poly(ethylene glycol) dimethacrylate (PEGDMA) as a difunctional crosslinker, and AHBPE as a multifunctional crosslinker were employed as printing resins to fabricate 5-fluorouracil- (5-FU) loaded tablets by digital light processing 3D printing. A D-optimal mixture design was applied to optimize the composition of printing resins and investigate the influence of the component on the printing time and drug release. Results showed that the printing time and drug release increased with increasing AA content but they decreased with the increase of AHBPE content. Addition of AA to the printing resins was necessary to achieve more complete drug release. The premature drug release was effectively inhibited by the incorporation of AHBPE. The tablet printed with a composition of 47.5 wt% of AA, 32.5 wt% of PEGDMA and 20.0 wt% of AHBPE had the lowest drug release of 13.96% at 2 h and highest one of 53.10% at 12 h, which were close to the model predicted values of 14.64 and 55.31%, respectively. It exhibited sustained drug release over 24 h in simulated gastrointestinal fluid and followed anomalous transport mechanism. The results suggest that AHBPE is a potential crosslinker for use in vat photopolymerization 3D printing of personalized drug delivery.