Osteoarthritis: Pathology, Mouse Models, and Nanoparticle Injectable Systems for Targeted Treatment

Holyoak, Derek T.; Tian, Ye; Meulen, Marjolein C. H. van der; Singh, Ankur

doi:10.1007/s10439-016-1600-z

Cited by 33 publications

(34 citation statements)

References 91 publications

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“…Although the controversy about the size necessary to retain longer the particles in the joint cavity, preclinical studies clearly demonstrate that NPs can be effective for IA delivery. 44 The prescribed dose of anti-IL-6 in RA patients (for OA patients is not yet an available therapy) is around 8 mg/kg IV, which can be dramatically reduced using this system injected IA. Indeed, with 1 μg/mL of antibody immobilized in NPs the inflammatory scenario was significantly reduced.…”

Section: Acs Applied Materials and Interfacesmentioning

confidence: 99%

Interleukin-6 Neutralization by Antibodies Immobilized at the Surface of Polymeric Nanoparticles as a Therapeutic Strategy for Arthritic Diseases

Lima

Cunha

Carvalho

et al. 2018

ACS Appl. Mater. Interfaces

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Arthritic diseases are disabling conditions affecting millions of patients worldwide. Pro-inflammatory cytokines, particularly interleukin-6 (IL-6), plays a crucial role in inflammation and cartilage destruction. Although the beneficial effects of antibody therapy, its efficacy is limited. Therefore, this work proposes the immobilization of antibodies at the surface of biodegradable polymeric nanoparticles (NPs) to capture and neutralize IL-6. Our system is intended to protect, extend and enhance the therapeutic efficacy after delivery. Chitosan-hyaluronic acid NPs are synthesized as a stable monodisperse population. After determining the maximum immobilization capacity (10 μg/mL), the capture ability was confirmed. Biological assays demonstrate the NPs cytocompatibility with human articular chondrocytes (hACs) and human macrophages. hACs stimulated with macrophage conditioned medium shows the beneficial role of IL-6 capture and neutralization. Biofunctionalized NPs exhibit a prolonged action and stronger efficacy than the free antibody. In conclusion, this system can be an effective and long lasting treatment for arthritic diseases.

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Section: Acs Applied Materials and Interfacesmentioning

confidence: 99%

Interleukin-6 Neutralization by Antibodies Immobilized at the Surface of Polymeric Nanoparticles as a Therapeutic Strategy for Arthritic Diseases

Lima

Cunha

Carvalho

et al. 2018

ACS Appl. Mater. Interfaces

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“…However, triggering by one stimulus usually suffer from 'false positive' or narrow responsive range in the in vivo microenvironments which are dynamically complex and contain various interfering signals. In addition, the carriers used in the most drug systems for OA exhibit unsatisfactory biocompatibility, low degradability, or poor penetration to vascular cartilage with highly dense extracellular matrix (ECM) [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

MMP-13 Enzyme and pH Responsive Theranostic Nanoplatform for Osteoarthritis

Lan

Chen

Pang

et al. 2020

Preprint

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Stimulus-responsive therapy permits precise control of therapeutic effect only at lesion of interest, which determines it a promising method for diagnosis and imaging-guided precision therapy. The acid environment and overexpressed matrix metalloproteinases-13 (MMP-13) are typical markers in osteoarthritis (OA). However, stimulus-responsive therapeutic platform with high specificity for OA basing on the two markers has not been developed yet. We herein demonstrate a new stimuli-responsive theranostic strategy against OA based on a novel multifunctional nano-micelle which is rationally designed and yet readily synthesized. Such nanoplatform is incorporated with a motif specifically targeting on cartilage, a motif responsive to matrix metalloproteinases-13 to specifically report OA condition and biodynamics of nano-micelles, an anti-inflammatory drug (e.g., psoralidin (PSO)) from traditional Chinese medicine, and a biocompatible polymeric skeleton for sustainable drug release in response to the acidic OA condition. The high effectiveness of this targeted precision therapy is demonstrated comprehensively by both in vitro an in vivo evidences.

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“…Although bisphosphonates were effective in attenuating OA progression in preclinical post-traumatic OA models, clinical studies in human subjects failed to show attenuation of cartilage loss assessed radiographically, despite the evidence that the treatment inhibited bone remodeling 24,25 . The discrepancies in the efficacy of bisphosphonates between preclinical and clinical models could be due to multiple factors including the use of invasive injury to induce OA in the animal models and the diverse stages of OA progression in the patient cohorts at the time of treatment intervention 26 . Previous studies examining the effect of inhibiting bone remodeling with bisphosphonates on attenuating OA disease progression have not used a controlled, non-invasive, preclinical OA model.…”

Section: Introductionmentioning

confidence: 99%

Role of subchondral bone properties and changes in development of load-induced osteoarthritis in mice

Adebayo

Park

et al. 2017

Osteoarthritis and Cartilage

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Objective Animal models recapitulating post-traumatic osteoarthritis (OA) suggest that subchondral bone (SCB) properties and remodeling may play major roles in disease initiation and progression. Thus, we investigated the role of SCB properties and its effects on load-induced OA progression by applying a tibial loading model on two distinct mouse strains treated with alendronate (ALN). Design Cyclic compression was applied to the left tibia of 26-week-old male C57Bl/6 (B6, low bone mass) and FVB (high bone mass) mice. Mice were treated with ALN (26μg/kg/day) or vehicle (VEH) for loading durations of 1, 2, or 6 weeks. Changes in articular cartilage and subchondral and epiphyseal cancellous bone were analyzed using histology and microcomputed tomography. Results FVB mice exhibited thicker cartilage, a thicker SCB plate, and higher epiphyseal cancellous bone mass and tissue mineral density than B6 mice. Loading induced cartilage pathology, osteophyte formation, and SCB changes; however, lower initial SCB mass and stiffness in B6 mice did not attenuate load-induced OA severity compared to FVB mice. In contrast, FVB mice exhibited less cartilage damage, and slower-growing and less mature osteophytes. In B6 mice, inhibiting bone remodeling via ALN treatment exacerbated cartilage pathology after 6 weeks of loading, while in FVB mice, inhibiting bone remodeling protected limbs from load-induced cartilage loss. Conclusions Intrinsically lower SCB properties were not associated with attenuated load-induced cartilage loss. However, inhibiting bone remodeling produced differential patterns of OA pathology in animals with low compared to high SCB properties, indicating that these factors do influence load-induced OA progression.

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Osteoarthritis: Pathology, Mouse Models, and Nanoparticle Injectable Systems for Targeted Treatment

Cited by 33 publications

References 91 publications

Interleukin-6 Neutralization by Antibodies Immobilized at the Surface of Polymeric Nanoparticles as a Therapeutic Strategy for Arthritic Diseases

Interleukin-6 Neutralization by Antibodies Immobilized at the Surface of Polymeric Nanoparticles as a Therapeutic Strategy for Arthritic Diseases

MMP-13 Enzyme and pH Responsive Theranostic Nanoplatform for Osteoarthritis

Role of subchondral bone properties and changes in development of load-induced osteoarthritis in mice

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