Drug Delivery and Translational Research最新文献

{"title":"Double-coated PLGA nanoparticles with hierarchical surface architecture for CD44-targeted siRNA delivery.","authors":"Giuseppe Longobardi, Pini Shekhter, Claudia Conte, Ronit Satchi-Fainaro, Fabiana Quaglia","doi":"10.1007/s13346-026-02115-8","DOIUrl":"10.1007/s13346-026-02115-8","url":null,"abstract":"<p><p>Efficient delivery of small interfering RNA (siRNA) remains a materials challenge because it requires nanocarriers that stabilize polyanionic cargo, support cellular interactions, and enable cytosolic delivery. Although poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are used due to biocompatibility, biodegradability, and regulatory acceptance, siRNA delivery with PLGA requires interfacial engineering to meet these constraints. Here, a modular double-coated PLGA NP platform (dcNPs2.0) is developed and optimized for siRNA complexation, surface functionalization, and scalable manufacturing. The system comprises a PLGA core coated with a polyethyleneimine (PEI) interlayer to mediate siRNA binding, followed by a hyaluronic acid (HA) outer layer, which improves colloidal stability and promotes CD44-mediated uptake. Process optimization, including transition from batch nanoprecipitation to microfluidic fabrication, provides high yield, excellent reproducibility, narrow size distributions, and increased siRNA loading. X-ray photoelectron spectroscopy confirms hierarchical multilayer assembly. The optimized dcNPs2.0 formulation exhibited robust physicochemical stability during storage, in serum-containing media, and following lyophilization with appropriate cryoprotection. Functional evaluation of dcNPs2.0 demonstrated efficient HA-mediated cellular uptake and effective silencing following siRNA delivery in both two-dimensional monolayers and three-dimensional spheroids of MDA-MB-231 cells. Overall, this work establishes a scalable, rationally engineered PLGA nanoplatform that integrates extracellular targeting with intracellular delivery requirements for siRNA therapeutic applications.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3956-3971"},"PeriodicalIF":6.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of clinically approved lipid nanoparticles for intranasal siRNA delivery against SARS-CoV-2.","authors":"Yuan Zhang, Matt D Johansen, Scott Ledger, Rebecca Shipley, Guanshu Zhao, Ernest Moles, Stuart Turville, Pall Thordarson, Philip M Hansbro, Maria Kavallaris, Anthony D Kelleher, Chantelle L Ahlenstiel","doi":"10.1007/s13346-026-02076-y","DOIUrl":"10.1007/s13346-026-02076-y","url":null,"abstract":"<p><p>SARS-CoV-2 continues to circulate globally, with persistent hospitalizations, despite a successful global vaccination strategy. We have developed highly conserved, antiviral short interfering (si)RNA and demonstrated in vivo antiviral efficacy following intranasal treatment of mice with naked siRNA. To enhance antiviral efficacy and siRNA protection, in this study we investigated the use of LNP packaging to improve delivery and efficacy. We examined three clinically approved lipid nanoparticle (LNP) formulations that mimic the compositions of Alnylam's Onpattro (MC3), Moderna's Spikevax (SM-102), and Pfizer-BioNTech's Comirnaty (ALC-0315) RNA-based therapeutics, to identify the optimal formulation for antiviral siRNA therapeutic respiratory delivery and antiviral efficacy. All LNP formulations assessed showed successful delivery of siRNA to respiratory cells in vitro and provided effective silencing of siRNA targeted SARS-CoV-2 genes. However, the MC3-based LNP-siRNA (MC3 LNP-siRNA) treatment elicited the least off-target immune activation, with no induction of interferon stimulated genes. Additionally, the MC3 LNP-siRNA remained effective when administered 24 h post-infection, significantly reducing viral RNA levels in vitro. Chemical modification of siRNA with 2'‑O‑methyl incorporation further attenuated immune activation, without compromising efficacy. In vivo intranasal delivery of MC3 LNP-siRNA was generally well tolerated, with no adverse effects on body weight or pulmonary function at therapeutic doses, although mild pulmonary leukocyte infiltration was observed at higher or repeated doses. Our study demonstrates that LNP-encapsulated and chemically modified siRNAs can provide an effective and mutation-resilient antiviral strategy. This study compares clinically relevant LNP formulations for siRNA delivery to the respiratory tract, demonstrating that MC3-based LNPs offer a promising platform for safe and effective RNA therapeutic delivery.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3848-3871"},"PeriodicalIF":6.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of solvent choice during microfluidic manufacture on the in vivo performance of liposomal doxorubicin.","authors":"Sarah Lindsay, René Holm, Sanket Shah, Yvonne Perrie","doi":"10.1007/s13346-026-02062-4","DOIUrl":"10.1007/s13346-026-02062-4","url":null,"abstract":"<p><p>Microfluidics offers a reproducible approach to liposome manufacture; however, the impact of solvent choice on formulation performance remains underexplored. Here, we investigated whether solvent selection during microfluidic manufacturing influences liposome performance by assessing its effect on the drug release and biodistribution of liposomal doxorubicin, using rotary evaporation as a conventional method of comparison. PEGylated liposomes (DSPC:Chol:DSPE-PEG2000, 3:1:1 w/w) were prepared using a staggered herringbone microfluidic mixer, with lipids dissolved in either ethanol or Transcutol, and compared with liposomes produced by rotary evaporation and extrusion. All formulations were actively loaded with doxorubicin via an ammonium sulphate gradient, purified by tangential flow filtration, and characterised for size, polydispersity, and drug loading. The three formulations (two microfluidic (ethanol vs Transcutol) and one rotary evaporation control) were intravenously administered to Sprague-Dawley rats (1 mg/kg), and doxorubicin concentrations in plasma and tissues were quantified using LC-MS. Although solvent choice produced liposomes with broadly comparable physicochemical properties (~ 100-120 nm, PDI < 0.25, encapsulation > 90%), Transcutol-based microfluidic liposomes showed prolonged and higher concentrations of doxorubicin within the plasma and tissue samples compared with liposomes produced by ethanol microfluidics and rotary evaporation. By contrast, the manufacturing method alone (microfluidics using ethanol as the solvent versus rotary evaporation) did not significantly influence biodistribution. These findings highlight solvent selection as an important parameter in microfluidic liposome manufacture, demonstrating that matching standard critical quality attributes and in vitro release behaviour alone may be insufficient to ensure comparable in vivo performance.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3702-3713"},"PeriodicalIF":6.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymeric micelle delivery of a HER2-selective tyrosine kinase inhibitor for targeted breast cancer therapy.","authors":"Jain Koo, Hyewon Jeon, Jaehyun Cheong, Hyunjin Kim, Heeju Lee, Kyung Hoon Min, Kyung Taek Oh","doi":"10.1007/s13346-026-02220-8","DOIUrl":"https://doi.org/10.1007/s13346-026-02220-8","url":null,"abstract":"<p><p>This study aimed to evaluate the anticancer efficacy of a newly developed HER2-targeting small-molecule inhibitor, MKH066, and to overcome its limited aqueous solubility through encapsulation in polymeric micelles for HER2-positive breast cancer therapy. MKH066 exhibited significantly higher cytotoxicity in HER2-overexpressing BT-474 and SK-BR-3 cells than in MCF-7 and MDA-MB-231 cells. The mPEG_2K-PLLA_3K micelle (M4) was selected based on its particle size below 200 nm, low polydispersity index (0.08), and the highest drug loading content (9.1%). M4 exhibited a reduced critical micelle concentration (~ 38 µg/mL) after drug encapsulation, sustained drug release over 96 h, and significantly improved apoptosis induction in BT-474 cells. The in vivo biodistribution demonstrated greater and prolonged tumor accumulation after intravenous injection in MCF-7 and BT-474 tumor models. In vivo studies demonstrated that intravenously administered M4 significantly inhibited tumor growth and increased apoptosis in tumor tissues without noticeable systemic toxicity. These findings provide proof-of-concept that polymeric micelle formulation enables the translation of the preferential in vitro anticancer activity of poorly water-soluble MKH066 into systemic in vivo application.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting the lipid ratio in lipid nanoparticles: A comparison of OFAT and design of experiments approaches.","authors":"Jade Forrester, Eleanor Vaughan, Benjamin R Knappett, Yvonne Perrie","doi":"10.1007/s13346-026-02125-6","DOIUrl":"10.1007/s13346-026-02125-6","url":null,"abstract":"<p><p>Despite the clinical success of lipid nanoparticles (LNPs), formulation optimisation remains dominated by inherited lipid ratios and screening approaches that fail to capture the combined influence of composition and manufacturing process. In this study, one-factor-at-a-time (OFAT) and Design of Experiments (DoE) strategies were applied to investigate how lipid molar ratio influences critical quality attributes (CQAs) and mRNA expression. In addition, manually executed and automated microfluidic manufacturing methods were compared to assess their impact on formulation-performance relationships. Across all strategies, multiple formulations beyond the standard molar ratio achieved comparable physicochemical properties, including particle size < 120 nm, low polydispersity index (PDI < 0.2), and high encapsulation efficiency (> 75%). Differences in CQAs and expression profiles were observed between manually and automated microfluidic manufactured DoE formulations, indicating that both composition and process conditions influence formulation performance. DoE analysis revealed non-linear and process-dependent relationships between lipid composition and CQAs, with limited predictive capability within the explored design space, particularly for biological outputs. Comparison of OFAT and DoE datasets demonstrated that while OFAT identifies directional trends within a constrained design space, DoE provides broader insight into interaction effects and formulation trade-offs. Overall, these findings demonstrate that the conventional lipid ratio represents a robust but not necessarily optimal formulation and support a shift towards context-dependent, design-space-driven optimisation of LNP systems.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3972-3992"},"PeriodicalIF":6.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the dose: a clearance-enabled in vitro platform for evaluating local therapies.","authors":"Mandeep K Marway, Sahib K Marway, Michael B Celejewski, Anthony D D'Angelo, Boyang Zhang, Ryan G Wylie","doi":"10.1007/s13346-026-02060-6","DOIUrl":"10.1007/s13346-026-02060-6","url":null,"abstract":"<p><p>Inclusion of physiologically relevant clearance mechanisms into organ-on-a-chip models is essential to reproduce tissue exposure and predict therapeutic efficacy, especially for local therapies and drug delivery applications that are already common in the clinic for ocular and cancer treatments. There remains a need for clearance-enabled organ-on-a-chips amenable to high throughput screening, especially with the emerging trend to expedite formulation and drug delivery vehicle (DDV) design with machine learning. To address this gap, we developed a microfluidic platform that incorporates continuous, pressure-driven clearance through interconnected microchannels and three-dimensional (3D) systems, enabling translational evaluation of local therapies and DDVs, such as injectable hydrogels, that aim to reduce systemic toxicity and enhance efficacy by prolonging drug residence at disease sites. In this study, fluorescent 4 and 65 kDa dextrans were used to confirm that pressure gradients across the platform promote efficient clearance versus passive diffusion. The pressure gradients were then applied to breast cancer spheroids co-cultured with macrophages in a fibrin hydrogel to evaluate the therapeutic efficacy of an interferon gamma (IFN-γ)-releasing agarose hydrogel in combination with anti-human epidermal growth factor receptor 2 (anti-HER2). Fluorescent imaging of spheroid area revealed increased cancer cell viability, lower drug efficacy, when continuous clearance was present, highlighting the impact of drug clearance. This study establishes the clearance-enabled microfluidic platform as a translationally relevant in vitro model for evaluating local therapies under continuous clearance, thereby bridging the gap between traditional static platforms and in vivo models for evaluating local pharmacokinetics and pharmacodynamics.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3658-3676"},"PeriodicalIF":6.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnetically controlled delivery capsule endoscopy for precise drug delivery to intestinal lesions.","authors":"Chen He, Xi Jiang, Ting Zhang, Yizhi Chen, Xiaoou Qiu, Zhaoshen Li, Zhuan Liao","doi":"10.1007/s13346-026-02066-0","DOIUrl":"10.1007/s13346-026-02066-0","url":null,"abstract":"<p><p>Current drug delivery devices can't deliver drugs toward targeted intestinal lesions non-invasively. A novel magnetically controlled delivery capsule endoscopy (MDCE) system was developed to accurately deliver topical therapy toward intestinal lesions under real-time optical visualization. We aimed to evaluate the feasibility and efficacy of this MDCE system in precisely targeted delivery of topical therapy. The delivery feasibility of the MDCE were first evaluated using an ex vivo swine intestinal model. In this model, simulated lesions (n = 27) were created and marked with a pre-selected dye (0.1% methylene blue). The MDCE delivery processes for small intestine lesions were conducted in four Bama miniature pigs. The feasibility of MDCE was defined as successful drug delivery to specific simulated small bowel lesion under optical surveillance. Efficacy was evaluated using parameters including image quality, maneuverability of the MDCE, and the time required for aiming and drug delivery taken by MDCE. The MDCE system demonstrated robust feasibility in an ex vivo intestinal model, achieving over 80% targeting success rate across 27 lesions at various orientations. This precision was successfully translated in vivo, with 91.7% (22/24) of target lesions precisely stained. Except for two raised lesions, 22 of them were precisely stained. The image quality and the maneuverability of the MDCE system were both graded as the best. Further analysis of procedural efficiency revealed that while the time for aiming lesions (16 s to 191 s) was longer in the small intestine than in the colon, especially when aiming at flat lesions (p = 0.0304), the rapid dye delivery time (4 s to 11 s) remained consistent across all locations and lesion types (p > 0.05). This study confirmed the feasibility and efficacy of the MDCE system for delivering targeted drug to specific intestinal lesions with real-time, vision-based monitoring in swine models.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3783-3791"},"PeriodicalIF":6.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Technical pen-based printhead for high-precision microdosing of personalized therapies.","authors":"Paola Carou-Senra, Carlos Rial, Alex Richter, Abdul W Basit, Carmen Alvarez-Lorenzo, Alvaro Goyanes","doi":"10.1007/s13346-026-02065-1","DOIUrl":"10.1007/s13346-026-02065-1","url":null,"abstract":"<p><p>Additive manufacturing offers unprecedented opportunities for personalized medicine, but most pharmaceutical printing platforms are optimized for milligram-range doses, limiting their suitability for microdosing. This work introduces a novel liquid deposition approach using a modified technical pen integrated into a pharmaceutical printer. The gravity-driven mechanism enabled precise microscale dispensing without external thermal, pneumatic, or electrical inputs, which have been associated with molecular stress in other printing technologies. Desmopressin, a potent synthetic hormone indicated for diabetes insipidus and requiring ultra-low doses, was selected as a model compound. Oral films (2 × 4 cm) containing therapeutically relevant doses (33-134 µg) were produced by depositing up to four layers of pharmaceutical ink. A custom-developed software interface allowed precise control of key process parameters, supporting reproducibility and automated workflows. The system achieved ~ 100% dose accuracy, with a strong correlation between drug content and layer number. Films exhibited rapid disintegration and immediate release. Stability testing showed no drug degradation over one month. Unlike more complex printing platforms, the technical printhead architecture offered straightforward manipulation and rapid setup. Given the constant ink flow rate and low, consistent, deposition volumes, only 1 mL of formulation is sufficient to produce up to 238 single-layer 2 × 4 cm films. These findings position the technical pen-based printhead as a promising, precise, and cost-effective addition to the additive manufacturing landscape, with strong potential for low-dose personalized pharmaceutical applications, including biologics. Moreover, its performance underscores the potential for further optimization and broader application.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3746-3760"},"PeriodicalIF":6.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbubble-free mechanical sonoporation for MR-guided drug delivery in solid tumours: a proof-of-concept study.","authors":"Deyssy Patrucco, Martina Capozza, Francesca Garello, Alberto Mangia, Carla Carrera, Giulia Tarso, Enzo Terreno","doi":"10.1007/s13346-026-02078-w","DOIUrl":"10.1007/s13346-026-02078-w","url":null,"abstract":"<p><p>Ultrasound (US)-mediated drug delivery is a promising strategy for localised, minimally invasive molecular transport, typically relying on microbubble-assisted sonoporation. However, clinical translation is limited by the short half-life, cost, and cytotoxicity of exogenous microbubbles. In this proof-of-concept study, we present a microbubble-free, mechanically driven sonoporation approach for intracellular delivery of hydrophilic agents, monitored non-invasively by magnetic resonance imaging (MRI). Using a low-intensity, non-focused ultrasound protocol (1 MHz, MI 0.25, 25% duty cycle, 1 Hz PRF) we achieved efficient intracellular internalisation of the MRI contrast agent Gadoteridol (~ 7 × 10⁹ Gd ions/cell) in vitro while maintaining > 70% cell viability and demonstrating complete membrane resealing within 30 min. Co-delivery with propidium iodide (PI) was confirmed by fluorescence microscopy and MRI, showing cytosolic distribution with negligible passive uptake in non-sonoporated controls. Compared to established permeabilisation methods (electroporation, pinocytosis, hypotonic swelling), microbubble-free sonoporation produced higher uptake with lower oxidative stress. In vivo experiments in K562 tumour-bearing mice showed that intravenous co-administration of Gadoteridol and PI followed by local sonoporation yielded significantly enhanced and prolonged T1 MRI contrast and increased intratumoural accumulation of both agents. These findings establish microbubble-free sonoporation as an effective, controllable technique for intracellular delivery, with the added benefit of MRI-based monitoring. This strategy addresses key limitations of microbubble-based methods and holds strong potential for image-guided therapeutic applications in solid tumors.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3888-3900"},"PeriodicalIF":6.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146225904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multi-compartment pulsatile drug delivery system for sequential release: in vitro and in vivo evaluation.","authors":"Seung-Dong Yoo, Yejin An, Gayoung Kim, Beom Soo Shin, Soyoung Shin","doi":"10.1007/s13346-026-02071-3","DOIUrl":"10.1007/s13346-026-02071-3","url":null,"abstract":"<p><p>This study presents an innovative, structurally engineered, pulsatile oral drug delivery platform that enables programmable, sequential drug release by integrating a structurally engineered three-dimensional (3D)-printed capsular device with conventional immediate-release (IR) tablets. Unlike coating-based or multilayer systems, which suffer from complex manufacturing and inconsistent release profiles, the multi-compartment capsule provides precise and reproducible control over the release timing through simple structural modifications. Each compartment accommodated intact IR tablets, allowing immediate release from the open-window sections and delayed release from the barrier-enclosed compartments. The lag time (T_lag) before drug release can be predictably tuned by adjusting the barrier wall thickness. The system was optimized for esomeprazole and naproxen, for which gastroprotection requires temporally separated exposure. The in vitro dissolution displayed immediate release of esomeprazole and delayed release of naproxen with T_lag of 11.33 ± 1.37 h. Both immediate absorption of esomeprazole and delayed absorption of naproxen were observed following oral administration in beagle dogs. The time to maximum plasma concentration (T_max) of esomeprazole was 0.67 ± 0.67 h, whereas the T_max of naproxen was 9.83 ± 2.40 h with a T_lag of 4.75 ± 1.17 h. These findings demonstrate that this modular 3D-printed platform, combined with conventional tablets, provides controlled and sequential drug delivery, thereby supporting patient-tailored therapeutic regimens.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3804-3816"},"PeriodicalIF":6.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}