Intra-articular delivery of sinomenium encapsulated by chitosan microspheres and photo-crosslinked GelMA hydrogel ameliorates osteoarthritis by effectively regulating autophagy

Chen, Pengfei; Chen, Xia; Mei, Sheng; Wang, Jiying; Shan, Zhi; Lin, Xianfeng; Fan, Shunwu

doi:10.1016/j.biomaterials.2015.12.006

Cited by 111 publications

(77 citation statements)

References 38 publications

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“…Recently, accumulating studies have demonstrated that chitosan could be used as a deliverer to deliver the drugs, genes, and proteins into the articular space to improve OA progression (Kaderli et al, 2015;Park et al, 2013;Patchornik et al, 2012;Rodríguez-Vázquez et al, 2015;Tan et al, 2009;). Chitosan could be prepared as various forms of an intraarticular injectable scaffold to crosslink with therapeutic molecules for the clinical application of OA treatment, for example, hyaluronic/chitosan hydrogels (Kaderli et al, 2015;Park et al, 2013;Patchornik et al, 2012;Tan et al, 2009), berberine or kartogenin/chitosan nanoparticles (Kang, Ko, Kim, & Im, 2014;Zhou et al, 2015), and sinomenium/chitosan microsphere (Chen et al, 2016). Chitosan could be prepared as various forms of an intraarticular injectable scaffold to crosslink with therapeutic molecules for the clinical application of OA treatment, for example, hyaluronic/chitosan hydrogels (Kaderli et al, 2015;Park et al, 2013;Patchornik et al, 2012;Tan et al, 2009), berberine or kartogenin/chitosan nanoparticles (Kang, Ko, Kim, & Im, 2014;Zhou et al, 2015), and sinomenium/chitosan microsphere (Chen et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Glucose adsorption to chitosan membranes increases proliferation of human chondrocyte via mammalian target of rapamycin complex 1 and sterol regulatory element‐binding protein‐1 signaling

Chang

Huang

Cheng

et al. 2017

Journal Cellular Physiology

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Osteoarthritis (OA) is currently still an irreversible degenerative disease of the articular cartilage. Recent, dextrose (d-glucose) intraarticular injection prolotherapy for OA patients has been reported to benefit the chondrogenic stimulation of damaged cartilage. However, the detailed mechanism of glucose's effect on cartilage repair remains unclear. Chitosan, a naturally derived polysaccharide, has recently been investigated as a surgical or dental dressing to control breeding. Therefore, in this study, glucose was adsorbed to chitosan membranes (CTS-Glc), and the study aimed to investigate whether CTS-Glc complex membranes could regulate the proliferation of human OA chondrocytes and to explore the underlying mechanism. Human OA and SW1353 chondrocytes were used in this study. The experiments involving the transfection of cells used SW1353 chondrocytes. A specific inhibitor and siRNAs were used to investigate the mechanism underlying the CTS-Glc-regulated proliferation of human chondrocytes. We found that CTS-Glc significantly increased the proliferation of both human OA and SW1353 chondrocytes comparable to glucose- or chitosan-only stimulation. The role of mammalian target of rapamycin complex 1 (mTORC1) signaling, including mTOR, raptor, and S6k proteins, has been demonstrated in the regulation of CTS-Glc-increased human chondrocyte proliferation. mTORC1 signaling increased the expression levels of maturated SREBP-1 and FASN and then induced the expressions of cell cycle regulators, that is, cyclin D, cyclin-dependent kinase-4 and -6 in human chondrocytes. This study elucidates the detailed mechanism behind the effect of CTS-Glc complex membranes in promoting chondrocyte proliferation and proposes a possible clinical application of the CTS-Glc complex in the dextrose intraarticular injection of OA prolotherapy in the future to attenuate the pain and discomfort of OA patients.

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Section: Discussionmentioning

confidence: 99%

Glucose adsorption to chitosan membranes increases proliferation of human chondrocyte via mammalian target of rapamycin complex 1 and sterol regulatory element‐binding protein‐1 signaling

Chang

Huang

Cheng

et al. 2017

Journal Cellular Physiology

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“…CMs are characterized by biocompatibility, nontoxicity, non-allergenic, and biodegradability; as a result, CMs can successfully provide site-specific drug delivery [23]. In this study, the hyaluronic acid methacrylate (HAMA) hydrogel was used as a vehicle to facilitate intra-articular injection of chitosan.…”

Section: Introductionmentioning

confidence: 99%

Photo-crosslinked HAMA hydrogel with cordycepin encapsulated chitosan microspheres for osteoarthritis treatment

Chen

Mei

et al. 2016

Oncotarget

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Autophagy is a protective mechanism in normal cartilage. The present study aimed to investigate the synergistic therapeutic effect of promotion of chondrocyte autophagy via exposure to cordycepin encapsulated by chitosan microspheres (CM-cordycepin) and photo-crosslinked hyaluronic acid methacrylate (HAMA) hydrogel, with the goal of evaluating CM-cordycepin as a treatment for patients with osteoarthritis. First, we developed and evaluated the characteristics of HAMA hydrogels and chitosan microspheres. Next, we measured the effect of cordycepin on cartilage matrix degradation induced by IL1-β in chondrocytes and an ex vivo model. Cordycepin protects cartilage from degradation partly by activation of autophagy. Moreover, we surgically induced osteoarthritis in mice, which were injected intra-articularly with CM-cordycepin and HAMA. The combination of CM-cordycepin and HAMA hydrogel retarded the progression of surgically induced OA. Cordycepin ameliorated cartilage matrix degradation at least partially by inducing autophagy in vivo. Our results demonstrate that the combination of cordycepin encapsulated by CMs and photo-crosslinked HAMA hydrogel could be a promising strategy for treating patients with osteoarthritis.

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“…For example, they are not antigenic, can be metabolized, have high stability and allow for high loading for water soluble active substances (Muller et al, 1996). Chitosan, a natural biodegradable polymer, is often used in the preparation of particular dosage forms (Bodmeier, Oh, Pramar, 1989;Aral, Akbuğa, 1998;Shu, Zhu, 2002;Norkar, Sher, Pawar, 2010;Sharma et al, 2012;Al-Qadi et al, 2012, Zhang, Wang, Pan, 2014Vivek et al, 2014;Koppolu et al, 2014;Xue et al, 2015;Chen et al, 2016;Ganguly, Kulkarni, Aminabhavi, 2016). A cationic linear bioamino polysaccharide, chitosan, is obtained by means of alkali distillation of chitin (Illum, 1998).…”

Section: Introductionmentioning

confidence: 99%

Investigation of the parameters affecting the release of flurbiprofen from chitosan microspheres

Tilkan

Özdemir

2018

Braz. J. Pharm. Sci.

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Flurbiprofen (FLB), a NSAID, widely used for preventing pain generally for arthritis or dental problems. In this study, FLB loaded chitosan microspheres were prepared by ionotropic gelation method. In this method, microspheres were formed by dropping chitosan solutions containing FLB into sodium alginate solutions including sodium tripolyphosphate (TPP). A variety of formulation parameters like drug:polymer ratio, drug concentration, polymer's molecular weight, polymer concentration, pH and the concentration of TPP solutions, drying method and stirring time were analyzed. The dissolution studies were performed in a shaking water bath in pH 7.4 phosphate buffer saline (PBS) at 37 °C. Laser diffractometer was used for particle size analysis, and scanning electron microscope (SEM) was used for morphological properties. Drug loading and loading efficiency were calculated by using UV spectrophotometer. The particles obtained were spherical with 0.7-1.3 mm size range, and the loading efficiency was approximately 21-79%. The dissolution studies conducted revealed that drug:polimer ratio and the polymer type and concentration affected the drug release from microspheres. It was observed that increasing the polymer concentration, polymer's molecular weight and TPP concentration decreased the FLB release from microspheres, which was according to Higuchi kinetics.

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Intra-articular delivery of sinomenium encapsulated by chitosan microspheres and photo-crosslinked GelMA hydrogel ameliorates osteoarthritis by effectively regulating autophagy

Cited by 111 publications

References 38 publications

Glucose adsorption to chitosan membranes increases proliferation of human chondrocyte via mammalian target of rapamycin complex 1 and sterol regulatory element‐binding protein‐1 signaling

Glucose adsorption to chitosan membranes increases proliferation of human chondrocyte via mammalian target of rapamycin complex 1 and sterol regulatory element‐binding protein‐1 signaling

Photo-crosslinked HAMA hydrogel with cordycepin encapsulated chitosan microspheres for osteoarthritis treatment

Investigation of the parameters affecting the release of flurbiprofen from chitosan microspheres

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