Liposomal targeting of glucocorticoids to the inflamed synovium inhibits cartilage matrix destruction during murine antigen-induced arthritis

Hofkens, Wouter; Storm, Gert; Berg, Wim B. van den; Lent, P.L. van

doi:10.1016/j.ijpharm.2011.02.060

Cited by 34 publications

(20 citation statements)

References 28 publications

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“…13 Studies have previously reported that liposomal encapsulation of RA drugs may improve drug accumulation in inflamed synovial tissue, but conventional liposomes often suffer from the shortcomings of instability, low encapsulation efficiency (EE), and limited drug delivery efficiency. 14 Ethosomes are a novel type of liposomes containing a high concentration of shortchain alcohols, including ethanol, propylene glycol, or even a mixture of ethanol and propylene glycol. [15][16][17] The addition of ethanol improves the deformability of vesicles, thus overcoming some of the disadvantages of the conventional liposomes, but also carries the risk of skin irritation.…”

Section: Introductionmentioning

confidence: 99%

Essential oil-mediated glycerosomes increase transdermal paeoniflorin delivery: optimization, characterization, and evaluation in vitro and in vivo

Zhang

et al. 2017

IJN

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In this study, a novel glycerosome carrier containing essential oils was prepared for topical administration of paeoniflorin (PF) to enhance its transdermal drug delivery and improve drug absorption in the synovium. The formulation of glycerosomes was optimized by a uniform design, and the final vehicle was composed of 5% (w/v) phospholipid, 0.6% (w/v) cholesterol, and 10% (v/v) glycerol, with 2% (v/v) Speranskia tuberculata essential oil (STO) as the transdermal enhancer. The in vitro transdermal flux of PF loaded in the STO-glycerosomes was 1.4-fold, 1.6-fold, and 1.7-fold higher than those of glycerosomes, liposomes, and tinctures, respectively. In vivo studies showed that the use of STO-glycerosomes was associated with a 3.1-fold greater accumulation of PF in the synovium than that of common glycerosomes. This finding was confirmed by in vivo imaging studies, which found that the fluorescence intensity of Cy5.5-loaded STO-glycerosomes in mice knee joints was 1.8-fold higher than that of the common glycerosomes 5 h after administration. The glycerosomes mediated by STO exhibited considerable skin permeability as well as improved drug absorption in the synovium, indicating that STO-glycerosomes may be a potential PF transdermal delivery vehicle for the treatment of rheumatoid arthritis caused by synovium lesions.

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Section: Introductionmentioning

confidence: 99%

Essential oil-mediated glycerosomes increase transdermal paeoniflorin delivery: optimization, characterization, and evaluation in vitro and in vivo

Zhang

et al. 2017

IJN

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“…31,32 Eventually, the drugs persisted in extravascular space, mainly devoured by the macrophages in the synovial layer. [33][34][35][36] The TP encapsulation ratio was detected by high-performance liquid chromatography method, and the EE of TP in PPT was 48.6%. The nano size and the zeta potential make it promising for the treatment of RA.…”

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confidence: 99%

Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo

Zhang

Wang

et al. 2016

IJN

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Triptolide (TP) displays a strong immunosuppression function in immune-mediated diseases, especially in the treatment of rheumatoid arthritis. However, in addition to its medical and health-related functions, TP also exhibits diverse pharmacological side effects, for instance, liver and kidney toxicity and myelosuppression. In order to reduce the side effects, a nano drug carrier system (γ-PGA- l -PAE-TP [PPT]), in which TP was loaded by a poly-γ-glutamic acid-grafted l -phenylalanine ethylester copolymer, was developed. PPT was characterized by photon scattering correlation spectroscopy and transmission electron microscopy, which demonstrated that the average diameter of the drug carrier system is 98±15 nm, the polydispersity index is 0.18, the zeta potential is −35 mV, and the TP encapsulation efficiency is 48.6% with a controlled release manner. The methylthiazolyldiphenyl-tetrazolium bromide assay and flow cytometry revealed that PPT could decrease toxicity and apoptosis induced by free TP on RAW264.7 cells, respectively. The detection of reactive oxygen species showed that PPT could decrease the cellular reactive oxygen species induced by TP. Compared with the free TP-treated group, PPT improved the survival rate of the mice ( P <0.01) and had no side effects or toxic effects on the thymus index ( P >0.05) and spleen index ( P >0.05). The blood biochemical indexes revealed that PPT did not cause much damage to the kidney (blood urea nitrogen and creatinine), liver (serum alanine aminotransferase and aspartate aminotransferase), or blood cells ( P >0.05). Meanwhile, hematoxylin and eosin staining and terminal-deoxynucleotidyl transferase dUTP nick-end labeling staining indicated that PPT reduced the damage of free TP on the liver, kidney, and spleen. Our results demonstrated that PPT reduced free TP toxicity in vitro and in vivo and that it is a promising fundamental drug delivery system for rheumatoid arthritis treatment.

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“…MT-MMP-6, that are able to cleave BM components from playing a role in BM degradation, buthave yet to be studied (Hernandez-Barrantes, et al 2002), nor does it rule out the involvement of MMP-1 and MMP-13; both of which have increased gene expression in carbohydrate-induced laminitis and may play a role in laminitis pathophysiology (Wang et al 2014).TIMPs are multifunctional proteins and can act both as MMP activators and inhibitors (Zhao, et al 2004). TIMP-2 is able to bind and inhibit all MT- Additional enzymatic mediators of BM degradation are the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) proteases, many of which are involved in cartilage degradation in osteoarthritis (Hofkens et al 2011). ADAMTS-4 is capable of processing and destabilising the proteoglycans and glycoproteins of the lamellar BM.…”

Section: Theories On Laminitis Pathogenesismentioning

confidence: 99%

“…Evidence suggests that early treatment with dexamethasone reduces mortality among human septic shock patients (Cicarelli et al 2007). Recent evidence demonstrates glucocorticoids reduce protease (MMP and ADAMTS-4) expression and inhibit cartilage destruction in a mouse model of rheumatoid arthritis (Hofkens et al 2011). The link between systemic corticosteroid administration and the development of laminitis (Bailey 2010), and concern that their immunosuppressive effects may be detrimental to any concurrent septic disease has precluded their systemic use in clinical and experimental laminitis.…”

Section: Laminitis Prophylaxismentioning

confidence: 99%

“…Further work by the author has established that intravenous liposomes extravasate at sights of focal inflammation in the horse with a 24 fold increase in liposome levels in inflamed muscle compared to normal muscle at 24 hours post-injection . A recent report has described the successful application glucocorticoid liposomes in a mouse rheumatoid arthritis model (Hofkens et al 2011). In addition to clinical and histological improvement, ADAMTS-4 and MMP production by synovial cells was inhibited.…”

Section: Liposomesmentioning

confidence: 99%

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Drug delivery to equine digital lamellar tissue

Underwood¹

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Laminitis, a serious and debilitating disease of the equine foot, is a significant cause of wastage in the equine industry. There is no scientifically validated treatment and laminitis prophylaxis is currently limited to digital cryotherapy. Several key steps in laminitis pathophysiology have been elucidated, resulting in identification of drugs that may prevent laminitis (anti-laminitis drugs (ALDs)). Many of these pharmaceuticals are not suitable for systemic delivery but may be amenable to either local or nanoparticle delivery mechanisms.The aim of this thesis was to evaluate local, systemic and nanoparticle delivery mechanisms, using the matrix metalloproteinase (MMP) inhibitor marimastat, to establish a method of drug delivery that yields sustained therapeutic lamellar concentrations for experimental and potential clinical use. In order to establish marimastat concentrations necessary for inhibition of lamellar MMPs, zymography was performed using lamellar homogenates incubated in increasing concentrations of marimastat. Based on this assay, target marimastat concentrations of 177 ng/mL were set (the concentration necessary to inhibit 90% of lamellar MMP-2 and MMP-9).

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Liposomal targeting of glucocorticoids to the inflamed synovium inhibits cartilage matrix destruction during murine antigen-induced arthritis

Cited by 34 publications

References 28 publications

Essential oil-mediated glycerosomes increase transdermal paeoniflorin delivery: optimization, characterization, and evaluation in vitro and in vivo

Essential oil-mediated glycerosomes increase transdermal paeoniflorin delivery: optimization, characterization, and evaluation in vitro and in vivo

Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo

Drug delivery to equine digital lamellar tissue

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