The clearance and biodistribution of magnetic composite nanoparticles in healthy and osteoarthritic rat knees

Partain, Brittany D.; Unni, Mythreyi; Rinaldi, Carlos; Allen, Kyle D.

doi:10.1016/j.jconrel.2020.01.052

Cited by 24 publications

(16 citation statements)

References 53 publications

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“…In a rat OA model, increased particle retention (in 14 days) has been found in 15-month rat knees, compared to 5-and 10-month rat knees (Fig. 3c) [33]. Although no animal study precisely recapitulates how the pathophysiology of OA affects the clearance of nanoparticles from lymphatic pathway, we can speculate that the initial 'expansion' phase of lymphatic vessels during moderate experimental arthritis may facilitate efficient lymphatic clearance; in contrast, the collapsed phase of lymphatic vessel characterized by lymphatic vessel structural damage and loss of contraction may reduce lymphatic clearance of nanoparticle or their encapsulated drugs [17].…”

Section: Pharmacokinetics and Biodistribution Of Nanoparticlesmentioning

confidence: 79%

“…Synovial fluid and serum tend to equilibrate through synovium intercellular gaps in a normal status; in OA, synovial inflammation-associated increased capillary permeability facilitates the elimination of nanoparticles from joint [31]. However, the clearance of nanoparticles in OA joint is impaired compared with the healthy joint, which may be associated with synovial thickening [33,34]. Ageing associated metabolic changes, including less range of joint motion and decreased lubricating fluid, may also impede the clearance of nanoparticles.…”

Section: Pharmacokinetics and Biodistribution Of Nanoparticlesmentioning

confidence: 99%

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Nanoparticle–Cartilage Interaction: Pathology-Based Intra-articular Drug Delivery for Osteoarthritis Therapy

Dai

Guo

et al. 2021

Nano-Micro Lett.

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Osteoarthritis is the most prevalent chronic and debilitating joint disease, resulting in huge medical and socioeconomic burdens. Intra-articular administration of agents is clinically used for pain management. However, the effectiveness is inapparent caused by the rapid clearance of agents. To overcome this issue, nanoparticles as delivery systems hold considerable promise for local control of the pharmacokinetics of therapeutic agents. Given the therapeutic programs are inseparable from pathological progress of osteoarthritis, an ideal delivery system should allow the release of therapeutic agents upon specific features of disorders. In this review, we firstly introduce the pathological features of osteoarthritis and the design concept for accurate localization within cartilage for sustained drug release. Then, we review the interactions of nanoparticles with cartilage microenvironment and the rational design. Furthermore, we highlight advances in the therapeutic schemes according to the pathology signals. Finally, armed with an updated understanding of the pathological mechanisms, we place an emphasis on the development of “smart” bioresponsive and multiple modality nanoparticles on the near horizon to interact with the pathological signals. We anticipate that the exploration of nanoparticles by balancing the efficacy, safety, and complexity will lay down a solid foundation tangible for clinical translation.

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Section: Pharmacokinetics and Biodistribution Of Nanoparticlesmentioning

confidence: 79%

Section: Pharmacokinetics and Biodistribution Of Nanoparticlesmentioning

confidence: 99%

Nanoparticle–Cartilage Interaction: Pathology-Based Intra-articular Drug Delivery for Osteoarthritis Therapy

Dai

Guo

et al. 2021

Nano-Micro Lett.

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“…The number of rats in each group was chosen based on the calculation formula reported by Charan and Kantharia 20 . After a 1-week acclimation period, 24 rats underwent surgery for the radial transection of the medial meniscus to generate an OA model 21 , while the remaining 12 rats received a sham operation. Then, the rats were randomly grouped into either the 4 or 8 weeks of the sham, OA, or OA with CPS treatment (OA + CPS) groups ( n = 6, each group).…”

Section: Methodsmentioning

confidence: 99%

TRPV1 alleviates osteoarthritis by inhibiting M1 macrophage polarization via Ca2+/CaMKII/Nrf2 signaling pathway

Sun

et al. 2021

Cell Death Dis

118

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Osteoarthritis (OA) is the major course of joint deterioration, in which M1 macrophage-driven synovitis exacerbates the pathological process. However, precise therapies for M1 macrophage to decrease synovitis and attenuate OA progression have been scarcely proposed. Transient receptor potential vanilloid 1 (TRPV1) is a cation channel that has been implicated in pain perception and inflammation. In this study, we investigated the role of TRPV1 in the M1 macrophage polarization and pathogenesis of OA. We demonstrated that TRPV1 expression and M1 macrophage infiltration were simultaneously increased in both human and rat OA synovium. More than 90% of the infiltrated M1 macrophages expressed TRPV1. In the rat OA model, intra-articular injection of capsaicin (CPS), a specific TRPV1 agonist, significantly attenuated OA phenotypes, including joint swelling, synovitis, cartilage damage, and osteophyte formation. CPS treatment markedly reduced M1 macrophage infiltration in the synovium. Further mechanistic analyses showed that TRPV1-evoked Ca2+ influx promoted the phosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) and facilitated the nuclear localization of nuclear factor-erythroid 2-related factor 2 (Nrf2), which ultimately resulted in the inhibition of M1 macrophage polarization. Taken together, our findings establish that TRPV1 attenuates the progression of OA by inhibiting M1 macrophage polarization in synovium via the Ca2+/CaMKII/Nrf2 signaling pathway. These results highlight the effect of targeting TRPV1 for the development of a promising therapeutic strategy for OA.

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“…These vehicles have been shown to be susceptible to microvascular and synovial macrophage‐mediated drainage and can be retained in the joint space only for few weeks, depending on their size, charge and composition 9,64,76,77 . In fact, Partain et al determined that particles of around 190 nm in diameter, composed of poly(ethylene glycol)‐ploy(lactic acid) copolymer containing magnetic nanoparticles, can be retained for around 2 weeks after IA injection in a rat model of knee OA 78 . The use of larger particles that could better avoid lymphatic drainage and cell‐mediated particles elimination (Figure 1) is a potential strategy to achieve IA drug sustained release over longer periods of time.…”

Section: Intra‐articular Drug Delivery Strategies In Oamentioning

confidence: 99%

Biomaterial strategies for improved intra‐articular drug delivery

Castro

Garcı́a

Guldberg

2020

J Biomedical Materials Res

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Osteoarthritis (OA) is a joint degenerative disease that has become one of the leading causes of disability in the world. It is estimated that OA affects 50 million adults in the United States. Currently, there are no FDA‐approved treatments that slow OA progression and its treatment is limited to pain management strategies and life style changes. Despite the discovery of several disease‐modifying OA drugs (DMOADs) and promising results in preclinical studies, their clinical translation has been significantly limited because of poor intra‐articular (IA) bioavailability and challenges in delivering these compounds to tissues of interest within the joint. Here, we review current OA treatments and their effectiveness at reducing joint pain, as well as novel targets for OA treatment and the challenges related to their clinical translation. Moreover, we discuss intra‐articular (IA) drug delivery as a promising route of administration, describe its inherent challenges, and review recent advances in biomaterial‐based IA drug delivery for OA treatment. Finally, we highlight the potential of tissue targeting in the development of effective IA drug delivery systems.

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The clearance and biodistribution of magnetic composite nanoparticles in healthy and osteoarthritic rat knees

Cited by 24 publications

References 53 publications

Nanoparticle–Cartilage Interaction: Pathology-Based Intra-articular Drug Delivery for Osteoarthritis Therapy

Nanoparticle–Cartilage Interaction: Pathology-Based Intra-articular Drug Delivery for Osteoarthritis Therapy

TRPV1 alleviates osteoarthritis by inhibiting M1 macrophage polarization via Ca2+/CaMKII/Nrf2 signaling pathway

Biomaterial strategies for improved intra‐articular drug delivery

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