Hydrogel Doped with Sinomenine-CeO ₂ Nanoparticles for Sustained Intra-articular Therapy in Knee Osteoarthritis

Journal of drug targeting, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 32

Published: Jan. 2, 2025

Intra-articular injection has emerged as a promising approach for treating knee osteoarthritis (OA), showing notable efficacy and potential. However, the risk of side effects remains concern with commonly used steroid therapies in clinical practice. Here, we developed an intra-articular injectable hydrogel drug depot (SMN-CeO2@G) sustained OA treatment. This system, which carries sinomenine-loaded cerium dioxide nanoparticles (SMN-CeO2), enhances anti-inflammatory anti-apoptotic within joint cavity. SMN-CeO2@G features three-dimensional network structure approximate pore size 10 μm, stably encapsulating SMN-CeO2 (∼75 nm). Under hydrogen peroxide (H2O2) exposure simulated mechanical stress, achieves cumulative SMN release 44.72 ± 7.83% over 48 hours, demonstrating controlled capabilities. At concentration 0.5 μg/mL, significantly proliferation, reduces apoptosis, lowers matrix metalloproteinases-13 (MMP-13) secretion IL-1β-induced ATDC5 chondrocytes. In ATDC5-RAW264.7 co-culture model, effectively reactive oxygen species (ROS) levels, apoptosis (∼20%), MMP13 concentrations (24.3 3.1 ng/mL) chondrocytes, likely due to promotion macrophages M2 polarization. anti-OA vivo studies, single osteophyte formation, promotes subchondral bone normalization, alleviates pain sensitivity, serum IL-1β (59.3 2.4 pg/mL) MMP-13 (23.6 1.7 levels model rats. also prolonged retention synovial fluid, 6.7 2.8% still detectable at 72 hours post-injection, factor crucial therapeutic effect. Overall, presents tool treatment, potential improved outcomes.

Language: Английский

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Porcine-Derived Chondroitin Sulfate Sodium Alleviates Osteoarthritis in HTB-94 Cells and MIA-Induced SD Rat Models

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 521 - 521

Published: Jan. 9, 2025

Osteoarthritis (OA) is a chronic disease characterized by cartilage degradation, leading to bone friction, inflammation, stiffness, pain, and reduced mobility. This study investigates the therapeutic effects of porcine-derived chondroitin sulfate sodium (CS) on OA symptoms at both cellular animal levels. In vitro study, HTB-94 chondrocytes were treated with inflammatory stimuli CS (10, 50, 100, 200 μg/mL) assess release mediators expression genes proteins related synthesis degradation. vivo an MIA-induced rat model was used, (62, 124, 248 mg/kg b.w.) orally administered for 4 weeks. Key parameters, such as exercise capacity, micro-CT, histological evaluation joint tissues, serum markers, mRNA (inflammatory, apoptosis markers), analyzed. Porcine-derived significantly PGE2, NO, extracellular matrix degradation marker (COMP CTX-II) levels increased synthesis-related in cells rats. Additionally, modulated pathways notably inhibited vivo. The porcine comparable NSAID ibuprofen, demonstrating its potential anti-inflammatory chondroprotective agent management dietary supplementation.

Language: Английский

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Metal ion-crosslinking multifunctional hydrogel microspheres with inflammatory immune regulation for cartilage regeneration

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 28, 2025

Introduction Osteoarthritis (OA) is a degenerative disease of the joints characterized by cartilage degradation and synovial inflammation. Due to complex pathogenesis OA, multifaceted therapies that modulate inflammatory immune microenvironmental disturbances while promoting regeneration are key control progression OA. Methods Herein, multifunctional nanoparticle (DIC/Mg-PDA NPs) was constructed successfully metal chelation effect between Mg 2+ catecholamine bond from dopamine, followed amidation with diclofenac (DIC), which then prepared into an injectable hydrogel microsphere (DIC/Mg-PDA@HM) immune-regulating cartilage-repairing abilities through microfluidic technology for treatment osteoarthritis. Results discussion The sustained release composite microspheres achieved regulation converting macrophages M1 M2 promoted differentiation BMSCs. Moreover, enhanced DIC polydopamine (PDA) effectively downregulated factors, finally OA therapy. In addition, in vivo MRI tissue section staining model proved significant efficacy on conclusion, these novel demonstrated promising prospect multidisciplinary repairing

Language: Английский

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Microenvironment-Responsive Hydrogels Comprising Engineering Zeolitic Imidazolate Framework-8-Anchored Parathyroid Hormone-Related Peptide-1 for Osteoarthritis Therapy

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Intra-articular drug injections are effective for osteoarthritis (OA), but challenges such as the complex microenvironment and rapid diffusion require frequent injections. Herein, we propose a biofunctional hydrogel-based strategy prolonged delivery remodeling. We to functionalize zeolitic imidazolate framework-8 with tannic acid (TA-ZIF), anchor PTH-related peptide-1 (PTHrP-1) within this framework (TA-ZIF@P1) incorporate phenylboronic acid-modified gelatin-based hydrogel (GP hydrogel) system (GP@TA-ZIF@P1, GPTP responsive release properties that respond pathological microenvironments of OA. The facilitated controlled, sustained PTHrP-1 via dynamic boronic esters, in vitro vivo studies showing continuous over 28 days. It not only promotes chondrocyte proliferation also exhibits significant cytoprotective effects under hyperactive ROS IL-1β-induced conditions. Notably, transcriptome sequencing confirms facilitates both chondrogenesis inflammatory conditions by deactivating Wnt/β-Catenin signaling pathways enhancing PI3K/AKT pathway. Additionally, delays catabolic metabolism cartilage explants from mice environments. In surgical model mouse OA, show intra-articular injection hydrogels reduced periarticular bone remodeling promoted production glycosaminoglycans while offering chondroprotection against degeneration. To sum up, pioneering research on treatment combined system, offers valuable insights paradigm controlled PTHrP-1, representing advancement OA strategies.

Language: Английский

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Reprogramming peritoneal macrophages with outer membrane vesicle-coated PLGA nanoparticles for endometriosis prevention

Biomaterials, Journal Year: 2025, Volume and Issue: 319, P. 123198 - 123198

Published: Feb. 17, 2025

Language: Английский

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Copper silicate nanoparticle-mediated delivery of astragaloside-IV for osteoarthritis treatment by remodeling the articular cartilage microenvironment

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown, P. 113583 - 113583

Published: March 1, 2025

Language: Английский

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Leveraging engineered yeast small extracellular vesicles serve as multifunctional platforms for effectively loading methyl salicylate through the “esterase-responsive active loading” strategy

European Journal of Pharmaceutics and Biopharmaceutics, Journal Year: 2025, Volume and Issue: unknown, P. 114696 - 114696

Published: March 1, 2025

Language: Английский

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Intelligent Nanomaterials Design for Osteoarthritis Managements

Small Methods, Journal Year: 2025, Volume and Issue: unknown

Published: March 30, 2025

Osteoarthritis (OA) is the most prevalent degenerative joint disorder, characterized by progressive degradation, pain, and diminished mobility, all of which collectively impair patients' quality life escalate healthcare expenditures. Current treatment options are often inadequate due to limited efficacy, adverse side effects, temporary symptom relief, underscoring urgent need for more effective therapeutic strategies. Recent advancements in nanomaterials nanomedicines offer promising solutions improving drug bioavailability, reducing effects providing targeted benefits. This review critically examines pathogenesis OA, highlights limitations existing treatments, explores latest innovations intelligent design OA therapy, with an emphasis on their engineered properties, mechanisms, translational potential clinical application. By compiling recent findings, this work aims inspire further exploration innovation nanomedicine, ultimately advancing development personalized therapies.

Language: Английский

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Sodium Hyaluronate‐PDGF Repairs Cartilage and Subchondral Bone Microenvironment via HIF‐1α‐VEGF‐Notch and SDF‐1‐CXCR4 Inhibition in Osteoarthritis

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(7)

Published: March 30, 2025

ABSTRACT Chronic degenerative changes in cartilage and subchondral bone that lead to instability of the microenvironment are essential for development osteoarthritis (OA) old. Synchronous repair may be a key strategy OA treatment. PDGF‐BB effectively promoted chondrocyte regeneration angiogenesis. However, mechanisms by which affects delivery joint cavity need further explored. In this study, we used sodium hyaluronate deliver (SH‐PDGF) space aimed determine SH‐PDGF repairing stabilising microenvironment. research, determined pharmacokinetics cartilage. Moreover, investigated effects on identifying HIF‐VEGF‐Notch axis SDF‐1‐CXCR4 an rat model. The results showed increased cell viability, decreased HIF‐1α levels, inhibited inflammation improved matrix metabolism osteoarthritic chondrocytes under hyperoxic or hypoxic conditions. We also found similar simultaneously. had some advantages over prolonging injection interval decreasing time. These protective were mediated inhibition both HIF‐1α‐VEGF‐Notch axis. underlying include HIF‐1α‐VEGF‐Notch‐mediated vessel invasion axis‐mediated crosstalk between tissue.

Language: Английский

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Cartilage‐Penetrating Framework Nucleic Acid Nanoparticles Ameliorate Osteoarthritis by Promoting Drug Delivery and Chondrocyte Uptake

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Abstract Osteoarthritis (OA) is a chronic joint disease that causes gradual deterioration of articular cartilage. A major challenge in OA treatment the limited penetration and delivery efficiency drugs to cartilage chondrocytes due rapid clearance through synovial fluid joints osmotic barrier extracellular matrix (ECM). To address this issue, novel tetrahedral framework nucleic acid (tFNA)‐based nanomedicine system (tFNA‐2WL) first synthesized with excellent permeability perfect chondrocyte endocytosis properties. After being loaded ginsenoside Rb1 (Gin), tFNA‐2WL&Gin complex not only penetrates but also accumulates menisci, ligaments, capsules, thus prolonging residence time Gin rat knees. In vitro, effectively promotes chondrogenesis, inhibits degradation by reducing apoptosis, scavenges reactive oxygen species (ROS), outperforming free Gin. rats, restores gait, reduces osteophyte formation, inflammation hypertrophy, protects from further damage more than other nanomedicines. These results demonstrate feasibility tFNA‐2WL improving pharmacokinetics efficacy highlight favorable curative effects for OA, offering promising paradigm translational medicine.

Language: Английский

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