Sulforaphane–PLGA microspheres for the intra-articular treatment of osteoarthritis

Ko, Ji‐Yun; Choi, You-Jeong; Jeong, Geun-Jae; Im, Gun‐Il

doi:10.1016/j.biomaterials.2013.03.066

Cited by 69 publications

(36 citation statements)

References 30 publications

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“…PLA has been shown to be biocompatible in rabbit knees [61,62], polyethylene glycol (PEG), often combined with other polymers (e.g., polycaprolactone (PCL)) is biocompatible and able to control release characteristics of the incorporated drug [72][73][74][75], however, by far, the most used synthetic polymer is PLGA. This synthetic polymer has a good biocompatibility and is able to incorporate many different types of drugs [29,31,[35][36][37]39,[42][43][44][45][46]50,60,61,[72][73][74][76][77][78][79][80][81][82][83][84]. Several studies have been published on the incorporation of proteins in different DDSs, a common problem in the classical models (e.g., PLGA), however, is the initial burst release, which can cause local toxic drug concentrations, and the acidic breakdown products can influence protein stability followed by a very slow or no release at all [68,85,86].…”

Section: Polymersmentioning

confidence: 99%

Drugs and Polymers for Delivery Systems in OA Joints: Clinical Needs and Opportunities

et al. 2014

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Osteoarthritis (OA) is a big burden of disease worldwide and one of the most common causes of disability in the adult population. Currently applied therapies consist of physical therapy, oral medication, intra-articular injections, and surgical interventions, with the main goal being to reduce pain and improve function and quality of life. Intra-articular (IA) administration of drugs has potential benefits in OA treatment because it minimizes systemic bioavailability and side effects associated with oral administration of drugs without compromising the therapeutic effect in the joint. However, IA drug residence time is short and there is a clinical need for a vehicle that is able to provide a sustained release long enough for IA therapy to fulfill its promise. This review summarizes the use of different polymeric systems and the incorporated drugs for IA drug delivery in the osteoarthritic joint with a primary focus on clinical needs and opportunities.

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Section: Polymersmentioning

confidence: 99%

Drugs and Polymers for Delivery Systems in OA Joints: Clinical Needs and Opportunities

et al. 2014

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“…Due to its antioxidative potential, its ability to selectively induce activating phase II enzymes (17), and inhibit histone deacetylase activity (18 -20), SFN is predominantly studied for its anticarcinogenic and antimicrobial properties. Furthermore, recent studies suggest that SFN has potential beneficial effects for the treatment of diabetes type 1 and type 2 (21-23) as well as osteoarthritis (24,25) and rheumatoid arthritis. In the latter context, SFN was found to inhibit synovial hyperplasia and T-cell activation (26).…”

mentioning

confidence: 99%

Anabolic and Antiresorptive Modulation of Bone Homeostasis by the Epigenetic Modulator Sulforaphane, a Naturally Occurring Isothiocyanate

Thaler

Maurizi

Roschger

et al. 2016

Journal of Biological Chemistry

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Bone degenerative pathologies like osteoporosis may be initiated by age-related shifts in anabolic and catabolic responses that control bone homeostasis. Here we show that sulforaphane (SFN), a naturally occurring isothiocyanate, promotes osteoblast differentiation by epigenetic mechanisms. SFN enhances active DNA demethylation via Tet1 and Tet2 and promotes preosteoblast differentiation by enhancing extracellular matrix mineralization and the expression of osteoblastic markers (Runx2, Col1a1, Bglap2, Sp7, Atf4, and Alpl). SFN decreases the expression of the osteoclast activator receptor activator of nuclear factor-B ligand (RANKL) in osteocytes and mouse calvarial explants and preferentially induces apoptosis in preosteoclastic cells via up-regulation of the Tet1/Fas/Caspase 8 and Caspase 3/7 pathway. These mechanistic effects correlate with higher bone volume (ϳ20%) in both normal and ovariectomized mice treated with SFN for 5 weeks compared with untreated mice as determined by microcomputed tomography. This effect is due to a higher trabecular number in these mice. Importantly, no shifts in mineral density distribution are observed upon SFN treatment as measured by quantitative backscattered electron imaging. Our data indicate that the food-derived compound SFN epigenetically stimulates osteoblast activity and diminishes osteoclast bone resorption, shifting the balance of bone homeostasis and favoring bone acquisition and/or mitigation of bone resorption in vivo. Thus, SFN is a member of a new class of epigenetic compounds that could be considered for novel strategies to counteract osteoporosis.

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“…In addition to palliative treatments, anti-inflammatory agents have also been delivered through intra-articular means to treat OA inflammation [77–79]. By treating the synovial fluid and lining in addition to articular cartilage, the expression of major pro-inflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor-α (TNF-α) can be addressed and reduced [80–86]. However, the delivery of chondrogenic growth factors such as TGF-β and IGF-1 in an injection manner can effect unwanted changes in the host tissue due to uncontrolled presentation of these bioactive factors [87–91].…”

Section: Biologic Delivery Methodsmentioning

confidence: 99%

“…Such results indicate that charge properties can be leveraged in innovative nanoparticle designs for the rapid uptake and retention of nanocarriers throughout the entire cartilage layer. Within the context of anti-inflammatory strategies for cartilage repair, the use MP carriers as the controlled delivery vehicles for small anti-inflammatory agents is also a subject of great interest [86, 108, 142–144]. …”

Section: Biologic Delivery Methodsmentioning

confidence: 99%

Strategies for controlled delivery of biologics for cartilage repair

Lam

Kasper

et al. 2015

Advanced Drug Delivery Reviews

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The delivery of biologics is an important component in the treatment of osteoarthritis and the functional restoration of articular cartilage. Numerous factors have been implicated in the cartilage repair process, but the uncontrolled delivery of these factors may not only reduce their full reparative potential and can also cause unwanted morphological effects. It is therefore imperative to consider the type of biologic to be delivered, the method of delivery, and the temporal as well as spatial presentation of the biologic to achieve the desired effect in cartilage repair. Additionally, the delivery of a single factor may not be sufficient in guiding neo-tissue formation, motivating recent research towards the delivery of multiple factors. This review will discuss the roles of various biologics involved in cartilage repair and the different methods of delivery for appropriate healing responses. A number of spatiotemporal strategies will then be emphasized for the controlled delivery of single and multiple bioactive factors in both in vitro and in vivo cartilage tissue engineering applications.

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Sulforaphane–PLGA microspheres for the intra-articular treatment of osteoarthritis

Cited by 69 publications

References 30 publications

Drugs and Polymers for Delivery Systems in OA Joints: Clinical Needs and Opportunities

Drugs and Polymers for Delivery Systems in OA Joints: Clinical Needs and Opportunities

Anabolic and Antiresorptive Modulation of Bone Homeostasis by the Epigenetic Modulator Sulforaphane, a Naturally Occurring Isothiocyanate

Strategies for controlled delivery of biologics for cartilage repair

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