Pharmaceutical Research最新文献

{"title":"Quantitative Structural and Compositional Elucidation of Real-World Pharmaceutical Tablet Using Large Field-of-View, Correlative Microscopy-Tomography Techniques and AI-Enabled Image Analysis.","authors":"Yinshan Chen, Sruthika Baviriseaty, Prajwal Thool, Jonah Gautreau, Phillip D Yawman, Kellie Sluga, Jonathan Hau, Shawn Zhang, Chen Mao","doi":"10.1007/s11095-024-03812-0","DOIUrl":"10.1007/s11095-024-03812-0","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study is to present a correlative microscopy-tomography approach in conjunction with machine learning-based image segmentation techniques, with the goal of enabling quantitative structural and compositional elucidation of real-world pharmaceutical tablets.</p><p><strong>Methods: </strong>Specifically, the approach involves three sequential steps: 1) user-oriented tablet constituent identification and characterization using correlative mosaic field-of-view SEM and energy dispersive X-ray spectroscopy techniques, 2) phase contrast synchrotron X-ray micro-computed tomography (SyncCT) characterization of a large, representative volume of the tablet, and 3) constituent segmentation and quantification of the imaging data through user-guided, iterative supervised machine learning and deep learning.</p><p><strong>Results: </strong>This approach was implemented on a real-world tablet containing 15% API and multiple common excipients. A representative volumetric tablet image was obtained using SyncCT at a 0.36-µm resolution, from which constituent particles and pores were fully segmented and quantified. As validation, the derived tablet formulation composition and porosity agreed with the experimental values, despite the micrometer-scale particle and pore sizes. The approach also revealed the formation of ordered mixture inside the tablet. Notably, the image-derived size distributions of both the agglomerated microcrystalline cellulose and its primary particulate units matched the laser diffraction-based measurements of the as-is material. Key pore attributes including the pore size distribution, spatial anisotropy, and pore interconnectivity were also qualified.</p><p><strong>Conclusion: </strong>Overall, this study demonstrated that the correlative microscopy-tomography approach, by leveraging phase contrast SyncCT and AI-based image analysis, can deliver new, practically-useful structural and compositional information and facilitate more efficient formulation and process development of tablets.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"203-217"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952952","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":"High Content Image Analysis of Cellular Responses of the Murine J774A.1 Cell Line and Primary Human Cells Alveolar Macrophages to an Extended Panel of Pharmaceutical Agents.","authors":"Lysann Tietze, Laura Urbano, Stephan Eisenmann, Jacqueline Schwarzinger, Julia Kollan, Ben Forbes, Lea Ann Dailey, Gabriela Hädrich","doi":"10.1007/s11095-024-03806-y","DOIUrl":"10.1007/s11095-024-03806-y","url":null,"abstract":"<p><strong>Introduction: </strong>In vitro screening of macrophages for drug-induced effects, such as phospholipidosis, is useful for detecting potentially problematic compounds in the preclinical development of oral inhaled products. High-content image analysis (HCIA) is a multi-parameter approach for cytotoxicity screening. This study provides new insights into HCIA-derived response patterns of murine J774A.1 cells and primary human alveolar macrophages (hAM).</p><p><strong>Methods: </strong>Several compounds were compared with reference groups (cationic amphiphilic drugs and apoptosis inducers) at different concentrations (0.01 to 10 µM). After incubation, cells were stained with fluorescence markers and HCIA was performed (Cytation™ 5 Cell Imaging System). Ten parameters were analysed: non-adherent cells, increased or reduced mitochondrial activity, membrane permeability, cell area, nuclear area, polynucleated cells, vacuole area, neutral and phospholipid content. A new system of response categorisation was developed for data analysis.</p><p><strong>Results: </strong>Murine J774A.1 cells exhibited a drug-induced response pattern that was distinct to the corresponding pattern of hAM cells. Comparison with the literature revealed that primary cells (rat or human origin) have similar response patterns, while cell lines (mouse, rat or human) exhibited a different response pattern. Hierarchical clustering revealed toxicologically aligned clusters of compounds, suggesting potential use for understanding mechanisms of drug effects in cell lines and primary cells.</p><p><strong>Conclusions: </strong>Valuable information for selecting a suitable cell type for HCIA screening of macrophage responses to drug compounds is provided. All cell types were suitable for screening drug-induced phospholipidosis. Still, human primary alveolar macrophages responded differently to drug treatment compared to macrophage cell lines and may be required to evaluate broader response-patterns and mechanisms of toxicity.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"93-108"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952942","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 Novel Peptide Mapping Method Utilizing Cysteine as a Reducing Agent.","authors":"Jun-Ting Fang, Si-Tao Wang, Haibin Wang, Wei-Jie Fang","doi":"10.1007/s11095-024-03805-z","DOIUrl":"10.1007/s11095-024-03805-z","url":null,"abstract":"<p><strong>Purposes: </strong>In the peptide mapping reduction process for monoclonal antibodies (mAbs) and other proteins, the conventional reducing reagents β-mercaptoethanol (β-ME) and dithiothreitol (DTT) pose challenges due to their strong odor and toxicity at high concentrations. Cysteine (Cys), an essential amino acid for new protein synthesis, is an overlooked, nontoxic, and odorless reducing agent. This study presents a novel peptide mapping method using Cys as the reducing agent.</p><p><strong>Methods: </strong>We explored the reducing effect of Cys at different concentrations and pH levels for peptide mapping analysis of a specific mAb (mAb-1), using DTT as a positive control. RP-HPLC analysis, including UV chromatogram comparison and overall similarity calculation, was conducted for comparison. LC-MS analysis was subsequently utilized to characterize the primary sequence of mAb-1. We also applied the method to other mAbs or proteins to demonstrate its wide applicability.</p><p><strong>Results: </strong>The UV chromatogram and overall similarity of Cys as a reducing agent at concentrations ranging from 10 to 40 mM and pH levels between 7.0 and 11.0 were consistent with those of the positive control. Reduced concentrations of Cys or lower pH levels compromised reducing efficacy. This novel reducing method proficiently characterized the primary sequence of mAb-1, achieving an overall sequence coverage of 97%. In the analysis of other mAbs or proteins, the peptide mapping results also showed high consistency.</p><p><strong>Conclusions: </strong>Cys exhibits a reducing ability comparable to DTT and possesses the advantageous characteristics of being nontoxic and odorless, making it a potential alternative for disulfide bond reduction and peptide mapping analysis of proteins and mAbs.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"173-184"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029214","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":"Rapid Development of High Concentration Protein Formulation Driven by High-Throughput Technologies.","authors":"Lun Xin, Monika Prorok, Zhe Zhang, Guilherme Barboza, Rahul More, Michael Bonfiglio, Lv Cheng, Kevin Robbie, Steven Ren, Yunsong Li","doi":"10.1007/s11095-024-03801-3","DOIUrl":"10.1007/s11095-024-03801-3","url":null,"abstract":"<p><strong>Background: </strong>High concentration protein formulation (HCPF) development needs to balance protein stability attributes such as conformational/colloidal stability, chemical stability, and solution properties such as viscosity and osmolality.</p><p><strong>Methodology: </strong>A three-phase design is established in this work. In Phase 1, conformational and colloidal stability are measured by 384-well-based high-throughput (HT) biophysical screening while viscosity reduction screening is performed with HT viscosity screening. Collectively, the biophysical and viscosity screening data are leveraged to design the phase 2 of short-term stability study, executed using 96-well plates under thermal and freeze/thaw stresses. In phase 2, samples are analyzed by stability-indicating assays and processed with pair-wise Student's t-test analyses to choose the final formulations. In phase 3, the final formulations are then confirmed through a one-month accelerated stability in glass vials.</p><p><strong>Results: </strong>Using a model antibody A (mAb-A), the initial HT screening successfully established the 384-well based platform. A lead formulation was chosen from the second round based on statistical analyses and subsequently tested against the commercial formulation of mAb-A as a control. Compared to the control, the lead formulation reduced the viscosity of mAb-A by 30% and decreased subvisible particles after thermal stress by 80%.</p><p><strong>Conclusions: </strong>HT biophysical screening in 384-well plates was demonstrated to effectively guide the rational design of a high-throughput stability screening study using 96-well plates. This platform enables the identification of a high concentration formulation within seven weeks within the first two phases of study that strategically balance stability with solution properties, thus achieving a rapid development of HCPF.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"151-171"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009729","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":"Deep Learning Prediction of Drug-Induced Liver Toxicity by Manifold Embedding of Quantum Information of Drug Molecules.","authors":"Tonglei Li, Jiaqing Li, Hongyi Jiang, David B Skiles","doi":"10.1007/s11095-024-03800-4","DOIUrl":"10.1007/s11095-024-03800-4","url":null,"abstract":"<p><strong>Purpose: </strong>Drug-induced liver injury, or DILI, affects numerous patients and also presents significant challenges in drug development. It has been attempted to predict DILI of a chemical by in silico approaches, including data-driven machine learning models. Herein, we report a recent DILI deep-learning effort that utilized our molecular representation concept by manifold embedding electronic attributes on a molecular surface.</p><p><strong>Methods: </strong>Local electronic attributes on a molecular surface were mapped to a lower-dimensional embedding of the surface manifold. Such an embedding was featurized in a matrix form and used in a deep-learning model as molecular input. The model was trained by a well-curated dataset and tested through cross-validations.</p><p><strong>Results: </strong>Our DILI prediction yielded superior results to the literature-reported efforts, suggesting that manifold embedding of electronic quantities on a molecular surface enables machine learning of molecular properties, including DILI.</p><p><strong>Conclusions: </strong>The concept encodes the quantum information of a molecule that governs intermolecular interactions, potentially facilitating the deep-learning model development and training.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"109-122"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813974","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":"Angelica gigas Nakai (Korean Dang-gui) Root Alcoholic Extracts in Health Promotion and Disease Therapy - active Phytochemicals and In Vivo Molecular Targets.","authors":"Junxuan Lü, Cheng Jiang, Joseph J Drabick, Monika Joshi, Stuthi Perimbeti","doi":"10.1007/s11095-024-03809-9","DOIUrl":"10.1007/s11095-024-03809-9","url":null,"abstract":"<p><p>Angelica gigas Nakai (AGN) root is a medicinal herbal widely used in traditional medicine in Korea. AGN root ethanolic extracts have been marketed as dietary supplements in the United States for memory health and pain management. We have recently reviewed the pharmacokinetics (PK) and first-pass hepatic metabolism of ingested AGN supplements in humans for the signature pyranocoumarins decursin (D, C_max 1x), decursinol angelate (DA, C_max ~ 10x) and their common botanical precursor and hepatic metabolite decursinol (DOH, C_max ~ 1000x). Here we update in vivo medicinal activities of AGN and/or its pyranocoumarins and furanocoumarin nodakenin in cancer, pain, memory loss, cerebral ischemia reperfusion stroke, metabolic syndrome and vascular endothelial dysfunctions, anxiety, sleep disorder, epilepsy, inflammatory bowel disease, osteoporosis and osteoarthritis. Given their polypharmacology nature, the pertinent mechanisms of action are likely misrepresented by many cell culture studies that did not consider the drug metabolism knowledge. We report here Rho-associated protein kinases (ROCK1/2) as novel targets for DA and DOH. Combining with published inhibitory activity of DOH on acetylcholinesterase, agonist activity of DOH and antagonist/degrader activity of DA/D on androgen and estrogen receptors, D/DA promoting activity for glutamic acid decarboxylase (GAD)- gamma-aminobutyric acid (GABA) inhibitory axis and inhibition of glutamate dehydrogenase (GDH), monoamine oxidase-A (MAO-A) and transient receptor potential vanilloid 1 (TRPV1), we postulate their contributions to neuro-cognitive, metabolic, oncologic, vascular and other beneficial bioactivities of AGN extracts. A clinical trial is being planned for an AGN extract to manage side effects of androgen deprivation therapy in prostate cancer patients.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"25-47"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952937","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":"An Amorphous Solid Dispersion of Baicalin and its Oral Therapeutic Effect on Ulcerative Colitis.","authors":"Yaxin Jia, Jiajia Gengji, Tao Gong, Zhirong Zhang, Li Deng","doi":"10.1007/s11095-024-03804-0","DOIUrl":"10.1007/s11095-024-03804-0","url":null,"abstract":"<p><strong>Objective: </strong>Ulcerative colitis (UC) treatment currently faces multiple challenges including adverse effects, prolonged therapy durations, and high costs. Baicalin (BA) has demonstrated anti-inflammatory benefits for inflammatory bowel disease, and the objective of this scholarly work is to address the challenges associated with the poor aqueous solubility and diminished oral bioavailability of the compound in question, thereby offering an innovative therapeutic approach for the management of ulcerative colitis.</p><p><strong>Methods: </strong>We developed a baicalin-arginine complex (BA-Arg) by screening for suitable basic compounds and utilizing a freeze-drying method, resulting in an amorphous solid dispersion of BA.</p><p><strong>Results: </strong>Our findings revealed that BA·Arg significantly enhances the intestinal absorption and transmembrane transport of BA without inducing toxicity in Caco-2 cells. Pharmacokinetic studies in healthy Wistar rats demonstrated significantly higher plasma concentrations of BA compared to free BA. In a mouse model induced by 3.5% dextran sodium sulfate, BA·Arg treatment markedly alleviated colitis symptoms as evidenced by reduced inflammatory cell infiltration, decreased lymphocyte aggregation in the colon, and better preservation of intestinal mucosa. This improved the overall anti-colitis efficacy of BA.</p><p><strong>Conclusions: </strong>Overall, our study presents a simple, eco-friendly formulation process that enhances BA solubility without the need for organic solvents, offering a practical and sustainable solution for developing BA-based therapies for UC.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2377-2389"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818940","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":"A Versatile, Low-Cost Modular Microfluidic System to Prepare Poly(Lactic-co-Glycolic Acid) Nanoparticles With Encapsulated Protein.","authors":"Malene Aaby Neustrup, Tom H M Ottenhoff, Wim Jiskoot, Joke A Bouwstra, Koen van der Maaden","doi":"10.1007/s11095-024-03792-1","DOIUrl":"10.1007/s11095-024-03792-1","url":null,"abstract":"<p><strong>Objective: </strong>Microfluidics has emerged as a promising technique to prepare nanoparticles. However, the current microfluidic devices are mainly chip-based and are often integrated into expensive systems that lack on-the-spot versatility. The aim of this study was to set up a modular microfluidic system based on low-cost capillaries and reusable, easy-to-clean building blocks that can prepare poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles with and without incorporated water-soluble biomacromolecules.</p><p><strong>Methods: </strong>A two-syringe system variant of the microfluidic system was set up to prepare PLGA particles and to investigate how the flow rates, solvents, and PLGA concentrations impacted the PLGA nanoparticle formation. A three-syringe system was designed to examine the incorporation of proteins into the PLGA particles.</p><p><strong>Results: </strong>The formation of the nanoparticles was affected by the PLGA concentration in the organic solvent, where an increasing concentration led to larger particle diameters (33-180 nm), and by the total flow rate, where an increase in the total flow rate led to smaller nanoparticles (197-77 nm). Using ultrapure water as the aqueous solvent resulted in precipitation at the outlet at higher PLGA concentrations. Aqueous poly(vinyl alcohol) created neutral particles in contrast to the negatively charged particles obtained with ultrapure water or an ethanol-water mixture. Incorporation of the proteins ovalbumin or lysozyme with a three-syringe system resulted in encapsulation efficiencies above 40%.</p><p><strong>Conclusion: </strong>A cheap and easily adjustable modular microfluidic system was developed to prepare PLGA nanoparticles with highly reproducible particle diameters that can effectively be loaded with proteins for drug and vaccine delivery.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2347-2361"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11682010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731828","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":"The Role of Artificial Intelligence and Machine Learning in Accelerating the Discovery and Development of Nanomedicine.","authors":"Vivek Agrahari, Yahya E Choonara, Mitra Mosharraf, Sravan Kumar Patel, Fan Zhang","doi":"10.1007/s11095-024-03798-9","DOIUrl":"10.1007/s11095-024-03798-9","url":null,"abstract":"<p><p>The unique potential of nanomedicine to address challenging health issues is rapidly advancing the field, leading to the generation of more effective products. However, these complex systems often pose several challenges with respect to their design for specific functionality, scalable manufacturing, characterization, quality control, and clinical translation. In this regard, the application of artificial intelligence (AI) and machine learning (ML) approaches can enable faster and more accurate data assessment, identifying trends and predicting outcomes, leading to efficient nanomedicine product development. This perspective paper discusses the potential of AI and ML in nanomedicine product development with a focus on their applications in discovery, assessment, manufacturing, and clinical trials. The potential limitations of AI and ML approaches in nanomedicine product development are also covered.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2289-2297"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771237","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":"Development and In-Vitro Evaluation of Doxorubicin-Loaded Methacrylate Gelatin (GelMa)-Acrylamide Hydrogels for the Treatment of Malignant Pleural Mesothelioma.","authors":"Nishant S Kulkarni, Gautam Chauhan, Mural Quadros, Dnyandev G Gadhave, Vivek Gupta","doi":"10.1007/s11095-024-03794-z","DOIUrl":"10.1007/s11095-024-03794-z","url":null,"abstract":"<p><strong>Objective: </strong>Malignant pleural mesothelioma (MPM) is the most prevalent subtype of malignant mesothelioma that affects the pleural lining of the lungs. Conventionally, chemotherapy via systemic injections has shown limited efficacy due to off-target effects, and inefficacious deposition at the disease site. In our previous study, we reported the development and optimization of UV-initiated methacrylate gelatin (GelMa)-acrylamide based hydrogel formulation for local intracavitary administration of therapies. The current study utilizes a pre-established GelMa formulation for delivering a small molecule chemotherapeutic agent, Doxorubicin (Dox), against in-vitro MPM models.</p><p><strong>Methods: </strong>Dox-loaded hydrogel (DLH) precursor solution was prepared by dissolving Dox in the precursor solution. The gels were characterized for physical properties such as gelling time, swelling index, bio adhesion, and injectability and were compared to blank hydrogels. Dox-loaded hydrogels were also tested for therapeutic efficacy in MPM cells in various 2D and 3D cell culture models.</p><p><strong>Results: </strong>It was revealed that Dox-loaded hydrogels retained similar physical properties, including gelling time (< 25 s), swelling index (~ 1,200%), bio-adhesion (> 20 g detachment force), and injectability (< 2N force for injecting precursor), compared to blank hydrogels. Moreover, the gel formulation effectively sustained the release of hydrophilic Dox HCl over a period of 12 days by increasing the degree of crosslinking between GelMa and its crosslinkers. Further, the therapeutic efficacy of Dox was retained even after loading into hydrogels, indicating that no chemical interactions took place between gel excipients and the drug. Studies in MPM cell-based models revealed that DLH showed excellent potential in inhibiting 2D and 3D cell growth, with DLH being more effective than plain Dox in suppressing tumor growth in 3D spheroid models.</p><p><strong>Conclusions: </strong>Overall, the results of the present study suggest that Dox-loaded hydrogels (DLH) may be a good candidate for efficacy study in preclinical mesothelioma models, with strong potential for clinical translation.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2331-2345"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780522","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}