3D-Printed Coaxial Hydrogel Patches with Mussel-Inspired Elements for Prolonged Release of Gemcitabine

Abstract

With the aim of fabricating drug-loaded implantable patches, a 3D printing technique was employed to produce novel coaxial hydrogel patches. The core-section of these patches contained a dopamine-modi?ed methacrylated alginate hydrogel loaded with a chemotherapeutic drug (Gemcitabine), while their shell section was solely comprised of a methacrylated alginate hydrogel. Subsequently, these patches were further modi?ed with CaCO3 cross linker and a polylactic acid (PLA) coating to facilitate prolonged release of the drug. Consequently, the results showed that additionofCaCO3 totheformulaenhancedthemechanicalpropertiesofthepatchesandsigni?cantly reduced their swelling ratio as compared to that for patches without CaCO3. Furthermore, addition of PLA coating to CaCO3-containing patches has further reduced their swelling ratio, which then signi?cantly slowed down the release of Gemcitabine, to a point where 4-layered patches could release the drug over a period of 7 days in vitro. Remarkably, it was shown that 3-layered and 4-layered Gemcitabine loaded patches were successful in inhibiting pancreatic cancer cell growth for aperiodof14dayswhentestedin vitro. Lastly,in vivoexperimentsshowedthatgemcitabine-loaded 4-layeredpatcheswerecapableofreducingthetumorgrowthrateandcausednoseveretoxicitywhen tested in mice. Altogether, 3D printed hydrogel patches might be used as biocompatible implants for local delivery of drugs to diseased site, to either shrink the tumor or to prevent the tumor recurrence after resection.