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.

Background: Powder-based 3D printing, an advanced additive manufacturing technique, can produce oral disintegrating tablets (ODTs) without disintegrants, creating larger-pored tablets via layer-by-layer powder stacking for better water absorption than traditional tablets. Methods: This study focused on using powder-based 3D printing to fabricate clozapine-based ODTs. Through central composite design (CCD), the formulation of ODTs was optimized for rapid disintegration. Analytical techniques such as X-ray Powder Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Differential Scanning Calorimetry (DSC) were employed to investigate the compatibility between clozapine and excipients. Results: The optimized 3D-printed ODTs exhibited a remarkably short disintegration time of (9.9 ± 0.7) s compared to (40) s for compressed tablets. The contact angle of the 3D-printed ODTs was measured as 60.48 ± 0.36°, indicating favorable wettability for disintegration. Scanning Electron Microscopy (SEM) analysis revealed a porous structure in 3D-printed tablets, with a porosity of 48.97% (over two times higher than that of compressed tablets as determined by mercury injection meter). Conclusions: Collectively, this finding demonstrates the feasibility of fabricating highly hydrophilic and non-distensible ODTs without disintegrants using powder-based 3D printing.

Precision therapy for ulcerative colitis (UC) relies on achieving sufficiently high drug concentrations at the site of inflammation. However, many natural anti-inflammatory small molecules, including β-sitosterol, exhibit inherent hydrophobicity and poor bioavailability, limiting their therapeutic potential. Conventional rectal dosage forms typically possess structurally fixed designs, making it difficult to precisely control the drug dose and release kinetics according to patient-specific therapeutic needs, thereby restricting clinical efficacy during local administration. To address these challenges, a β-sitosterol self-emulsifying lipid suppository was fabricated using semisolid extrusion (SSE) three-dimensional (3D) printing, and a programmable “structure-driven release” strategy was proposed for controllable drug delivery. The self-emulsifying Gelucire 44/14 matrix exhibited shear-thinning and thermoresponsive properties, enabling 3D printing under near-ambient conditions. Upon contact with physiological fluids, the suppository rapidly generated a stable oil-in-water nanoemulsion (self-emulsification time: 4.54 ± 0.17 min; droplet size: 386.16 ± 22.55 nm; polydispersity index: 0.26 ± 0.02), markedly improving the apparent solubility of the poorly water-soluble drug. Spectroscopic and thermodynamic analyses confirmed the stable molecular dispersion of the drug in the lipid matrix. Without altering the chemical composition, the release kinetics could be programmed through structural engineering. By precisely tuning the internal pore architecture and infill density of the printed suppository, the system enabled controllable transitions from rapid drug release to sustained release. This study establishes a structure-driven programmable delivery strategy that bridges 3D architectural design with pharmacokinetic regulation, exhibiting potential for the colon-targeted delivery of poorly soluble natural anti-inflammatory agents and for personalized therapy of mucosal inflammatory diseases, including UC.

Localized rectal delivery is a promising strategy for ulcerative colitis, as it may increase drug exposure at inflamed sites in the distal colorectum while reducing systemic exposure. However, many natural anti-inflammatory small molecules, including β-sitosterol, are hydrophobic and have poor aqueous dispersibility, limiting their formulation and therapeutic use. Conventional rectal dosage forms typically have fixed structures, making it difficult to tailor drug-release behavior. To address these challenges, a β-sitosterol-loaded self-emulsifying lipid suppository was fabricated using semisolid extrusion (SSE) three-dimensional (3D) printing, and the ability of the internal architecture to modulate early in vitro drug release was investigated. The Gelucire® 44/14-based matrix exhibited shear-thinning behavior and temperature-dependent softening, enabling SSE 3D printing. Upon contact with an aqueous medium, the printed suppositories formed submicron dispersions. Liquefaction and self-emulsification times ranged from 18.27 to 24.27 min and from 4.33 to 8.54 min, respectively. A representative formulation had a droplet size of 370.67 ± 39.09 nm and a polydispersity index of 0.27 ± 0.04. Fourier transform infrared, differential scanning calorimetry, and X-ray diffraction analyses indicated good drug–matrix compatibility and reduced β-sitosterol crystallinity, suggesting partial solubilization within the lipid matrix. With the matrix composition and external geometry held constant, in vitro release was adjusted by varying the internal pore architecture and nominal infill density. Lower-infill-density structures promoted faster medium penetration and earlier β-sitosterol release, whereas higher-infill-density structures slowed release by increasing structural resistance and diffusion-path tortuosity. These results demonstrate the feasibility of using SSE 3D printing to produce structure-modulated rectal dosage forms containing poorly water-soluble natural compounds.

Oral solid dosage forms, due to their mature manufacturing processes and stability, have become the cornerstone of clinical drug therapy. However, fixed dosages, uniform components, and large-scale production may not meet increasingly complex personalized requirements. The emergence of 3D-printed drugs provides a potential solution to this challenge. Drug 3D printing has progressed beyond feasibility verification and is moving toward functional dosage form design. Current research primarily focuses on printability; however, this review integrates printing technology, polymer functionality, structural design, release behavior, and translational requirements, summarizing mainstream printing technologies, including Fused Deposition Modeling (FDM), Direct Ink Writing/Semi-Solid Extrusion (DIW/SSE), Powder Bed Printing (SLS/BJ), and Photopolymerization (SLA/DLP). Polymers are classified according to drug release control functions, illustrating how modulation of porosity, filling density, shell thickness, material partitioning, and spatial drug distribution enables 3D-printed dosage forms with diverse therapeutic functions. These functions include immediate and sustained release, gastric retention, intestinal targeting, and sequential release of multiple components. This review provides guidance for technical selection, structural design, and formulation development of 3D-printed drugs, while highlighting major translational barriers, including limited printable excipients, empirical formulation development, insufficient structure-based release prediction, quality control challenges, and weak clinical evidence. Future progress requires close integration of material, process, structure, and performance, enabling 3D-printed drugs to evolve from individual prototypes into scalable, quality-controllable, and clinically translatable drug delivery systems.