3D‐Printed Lipid Mesophases for the Treatment of Chronic Liver Disease

Although lipid-based formulations are an attractive approach for enhancing the oral bioavailability of lipophilic drugs, their addition into solid oral dosage forms has been proven challenging due to their high viscosity and heat sensitivity. Therefore, unlike the traditional tableting process, this study employed semi-solid extrusion 3D-printing to produce–at room temperature–gastro-resistant printlets containing a high percentage of bioactive lipids for the effective delivery of lipophilic drugs through self-emulsification. The bio-compatible lipidic mesophase ink, owing to a tunable 3D nanostructure, is employed as a starting material to produce printlets via additive manufacturing. An active lipid mixture – with antifibrotic properties – is blended with the antioxidant vitamin E and water, and the ink printability is optimized by carefully tailoring its composition, and thus its phase identity. The obtained printlets disintegrated upon contact with intestinal fluids forming colloidal structures that enhanced the solubility of a poorly water-soluble drug. The printlets exhibited antifibrotic activity on human hepatic stellate cells, LX-2, suggesting that the generated self-emulsified colloidal structures made both the fibrosis-resolving bioactive excipients and the drug promptly available, enhancing their cell uptake and, in turn, their therapeutic activity.