The advantage of low-temperature forming through direct ink writing (DIW) 3D printing is becoming a strategy for the construction of innovative drug delivery systems (DDSs). Optimization of the complex formulation, including factors such as the printing ink, presence of solvents, and potential low mechanical strength, are challenges during process development. This study presents an application of DIW to fabricate water-soluble, high-dose, and sustained-release DDSs. Utilizing poorly compressible metformin hydrochloride as a model drug, a core-shell delivery system was developed, featuring a core composed of 96 % drug powder and 4 % binder, with a shell structure serving as a drug-release barrier. This design aligns with the sustained-release profile of traditional processes, achieving a 25.8 % reduction in volume and enhanced mechanical strength. The strategy facilitates sustained release of high-dose water-soluble formulations for over 12 h, potentially improving patient compliance by reducing formulation size. Process optimization and multi-batch flexibility were also explored in this study. Our findings provide a valuable reference for the development of innovative DDSs and 3D-printed drugs.

Cancer remains a disease with one of the highest mortality rates worldwide. The poor water solubility and tissue selectivity of commonly used chemotherapeutic agents contribute to their poor efficacy and serious adverse effects. This study proposes an alternative to the traditional physicochemically combined modifications used to develop targeted drug delivery systems, involving a simpler surface modification strategy. cRGDyK peptide (RGD)-modified PLGA nanoparticles (NPs) loaded with paclitaxel were constructed by coating the NP surfaces with polydopamine (PD). The average particle size of the produced NPs was 137.6 ± 2.9 nm, with an encapsulation rate of over 80%. In vitro release tests showed that the NPs had pH-responsive drug release properties. Cellular uptake experiments showed that the uptake of modified NPs by tumor cells was significantly better than that of unmodified NPs. A tumor cytotoxicity assay demonstrated that the modified NPs had a lower IC₅₀ and greater cytotoxicity than those of unmodified NPs and commercially available paclitaxel formulations. An in vitro cytotoxicity study indicated good biosafety. A tumor model in female BALB/c rats was established using murine-derived breast cancer 4T1 cells. RGD-modified NPs had the highest tumor-weight suppression rate, which was higher than that of the commercially available formulation. PTX-PD-RGD-NPs can overcome the limitations of antitumor drugs, reduce drug toxicity, and increase efficacy, showing promising potential in cancer therapy.