Therapeutic potential of hyaluronic acid/chitosan nanoparticles for the delivery of curcuminoid in knee osteoarthritis and an in vitro evaluation in chondrocytes

Wang,Jian; Wang,Xiang; Cao,Yun; Huang,Tao; Song,Deng‑Xin; Tao,Hai‑Rong

doi:10.3892/ijmm.2018.3817

Therapeutic potential of hyaluronic acid/chitosan nanoparticles for the delivery of curcuminoid in knee osteoarthritis and an in vitro evaluation in chondrocytes

Authors:
- Jian Wang
- Xiang Wang
- Yun Cao
- Tao Huang
- Deng‑Xin Song
- Hai‑Rong Tao
View Affiliations

Affiliations: Department of Orthopedics, Baoshan Branch of Shanghai First People's Hospital, Shanghai 200940, P.R. China, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999, P.R. China
Published online on: August 9, 2018 https://doi.org/10.3892/ijmm.2018.3817
Pages: 2604-2614
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Knee osteoarthritis (OA) is the main cause of leg pain in middle‑aged and elderly individuals. Hyaluronic acid (HA), as well as curcuminoid, has been used in the treatment of knee OA. In the present study, HA/chitosan nanoparticles (CNPs) were prepared for the delivery of curcuminoid, in order to investigate whether HA and curcuminoid can act synergistically as a better treatment option. The knee OA model was established by the Hulth method, and a knee OA chondrocyte model was constructed by the co‑induction of interleukin‑1β and tumor necrosis factor (TNF)‑α. The drug loading capacity of HA/CNP for the delivery of curcuminoid was measured by an ultraviolet assay, and the cytotoxicity to chondrocytes was measured by an MTT assay. Collagen II was detected by immunofluorescence, and the expression levels of nuclear factor (NF)‑κB and inflammation‑related genes in cartilage tissue and chondrocytes were detected. Chondrocyte proliferation was determined by an EdU assay, and chondrocyte apoptosis was determined by flow cytometry. The Mankin pathological score of the Outerbridge classification was obtained. The results demonstrated that the optimum drug loading capacity of HA/CNP for the delivery of curcuminoid was 38.44%, with a good sustained release function. HA/CNP treatment resulted in inhibition of the NF‑κB pathway, as well as the expression of matrix metalloproteinase (MMP)‑1 and MMP‑13, but it increased collagen II expression. HA/CNP for the delivery of curcuminoid significantly decreased the Outerbridge classification and Mankin pathological scores to close to normal until the 4th week. Furthermore, it was also observed that all the effects of HA/CNP on the delivery of curcuminoid were more prominent compared with the effects of HA or curcuminoid treatment individually. Taken together, these findings demonstrated that HA/CNP for the delivery of curcuminoid may suppress inflammation and chondrocyte apoptosis in knee OA via repression of the NF‑κB pathway.

View Figures

View References

1	Wu Q, Sun X and Du L: Association of fibulin-3 concentrations with the presence and severity of knee osteoarthritis: A cross-sectional study. Knee. 24:1369–1373. 2017. View Article : Google Scholar : PubMed/NCBI
2	Ogunbode AM, Adebusoye LA, Olowookere OO and Alonge TO: Physical functionality and self-rated health status of adult patients with knee osteoarthritis presenting in a primary care clinic. Ethiop J Health Sci. 24:319–328. 2014. View Article : Google Scholar :
3	Runhaar J, van Middelkoop M, Reijman M, Willemsen S, Oei EH, Vroegindeweij D, van Osch G, Koes B and Bierma-Zeinstra SM: Prevention of knee osteoarthritis in overweight females: The first preventive randomized controlled trial in osteoarthritis. Am J Med. 128:888–895.e4. 2015. View Article : Google Scholar : PubMed/NCBI
4	Ji B, Guo W, Ma H, Xu B, Mu W, Zhang Z, Amat A and Cao L: Isoliquiritigenin suppresses IL-1β induced apoptosis and inflammation in chondrocyte-like ATDC5 cells by inhibiting NF-κB and exerts chondroprotective effects on a mouse model of anterior cruciate ligament transection. Int J Mol Med. 40:1709–1718. 2017.PubMed/NCBI
5	Ricci M, Micheloni GM, Berti M, Perusi F, Sambugaro E, Vecchini E and Magnan B: Clinical comparison of oral administration and viscosupplementation of hyaluronic acid (HA) in early knee osteoarthritis. Musculoskelet Surg. 101:45–49. 2017. View Article : Google Scholar
6	Zhang Z, Leong DJ, Xu L, He Z, Wang A, Navati M, Kim SJ, Hirsh DM, Hardin JA, Cobelli NJ, et al: Curcumin slows osteoarthritis progression and relieves osteoarthritis-associated pain symptoms in a post-traumatic osteoarthritis mouse model. Arthritis Res Ther. 18:1282016. View Article : Google Scholar : PubMed/NCBI
7	Salwowska NM, Bebenek KA, Żądło DA and Wcisło- Dziadecka DL: Physiochemical properties and application of hyaluronic acid: A systematic review. J Cosmet Dermatol. 15:520–526. 2016. View Article : Google Scholar : PubMed/NCBI
8	Concoff A, Sancheti P, Niazi F, Shaw P and Rosen J: The efficacy of multiple versus single hyaluronic acid injections: A systematic review and meta-analysis. BMC Musculoskelet Disord. 18:5422017. View Article : Google Scholar : PubMed/NCBI
9	Li X, Feng K, Li J, Yu D, Fan Q, Tang T, Yao X and Wang X: Curcumin inhibits apoptosis of chondrocytes through activation ERK1/2 signaling pathways induced autophagy. Nutrients. 9:E4142017. View Article : Google Scholar : PubMed/NCBI
10	Wang F, Yang Y, Ju X, Udenigwe CC and He R: Polyelectrolyte complex nanoparticles from chitosan and acylated rapeseed cruciferin protein for curcumin delivery. J Agric Food Chem. 66:2685–2693. 2018. View Article : Google Scholar : PubMed/NCBI
11	Yu H, Nguyen MH and Hadinoto K: Effects of chitosan molecular weight on the physical and dissolution characteristics of amorphous curcumin-chitosan nanoparticle complex. Drug Dev Ind Pharm. 44:82–88. 2018. View Article : Google Scholar
12	Yasuda T: Type II collagen peptide stimulates Akt leading to nuclear factor-kappaB activation: Its inhibition by hyaluronan. Biomed Res. 35:193–199. 2014. View Article : Google Scholar
13	Yang Q, Wu S, Mao X, Wang W and Tai H: Inhibition effect of curcumin on TNF-α and MMP-13 expression induced by advanced glycation end products in chondrocytes. Pharmacology. 91:77–85. 2013. View Article : Google Scholar
14	Zhou L, Hu Y, Li C, Yan Y, Ao L, Yu B, Fang W, Liu J and Li Y: Levocorydalmine alleviates vincristine-induced neuropathic pain in mice by inhibiting an NF-kappa B-dependent CXCL1/CXCR2 signaling pathway. Neuropharmacology. 135:34–47. 2018. View Article : Google Scholar : PubMed/NCBI
15	Xu H, Bouta EM, Wood RW, Schwarz EM, Wang Y and Xing L: Utilization of longitudinal ultrasound to quantify joint soft-tissue changes in a mouse model of posttraumatic osteoarthritis. Bone Res. 5:170122017. View Article : Google Scholar : PubMed/NCBI
16	Xu J, Lu MX, Cui YD and Du YZ: Selection and evaluation of reference genes for expression analysis using qRT-PCR in Chilo suppressalis (Lepidoptera: Pyralidae). J Econ Entomol. 110:683–691. 2017.PubMed/NCBI
17	Xu Y, Asghar S, Yang L, Chen Z, Li H, Shi W, Li Y, Shi Q, Ping Q and Xiao Y: Nanoparticles based on chitosan hydrochloride/hyaluronic acid/PEG containing curcumin: In vitro evaluation and pharmacokinetics in rats. Int J Biol Macromol. 102:1083–1091. 2017. View Article : Google Scholar
18	Chen C, Zhang C, Cai L, Xie H, Hu W, Wang T, Lu D and Chen H: Baicalin suppresses IL-1β-induced expression of inflammatory cytokines via blocking NF-κB in human osteoarthritis chondrocytes and shows protective effect in mice osteoarthritis models. Int Immunopharmacol. 52:218–226. 2017. View Article : Google Scholar : PubMed/NCBI
19	Sharma M, Sahu K, Singh SP and Jain B: Wound healing activity of curcumin conjugated to hyaluronic acid: In vitro and in vivo evaluation. Artif Cells Nanomed Biotechnol. 46:1009–1017. 2018. View Article : Google Scholar
20	Zhuang Z, Ye G and Huang B: Kaempferol alleviates the interleukin-1β-induced inflammation in rat osteoarthritis chondrocytes via suppression of NF-κB. Med Sci Monit. 23:3925–3931. 2017. View Article : Google Scholar : PubMed/NCBI
21	De Palma A, Cheleschi S, Pascarelli NA, Giannotti S, Galeazzi M and Fioravanti A: Hydrostatic pressure as epigenetic modulator in chondrocyte cultures: A study on miRNA-155, miRNA-181a and miRNA-223 expression levels. J Biomech. 66:165–169. 2018. View Article : Google Scholar
22	Li Y, Wang J, Song X, Bai H, Ma T, Zhang Z, Li X, Jiang R, Wang G, Fan X, et al: Effects of baicalein on IL-1β-induced inflammation and apoptosis in rat articular chondrocytes. Oncotarget. 8:90781–90795. 2017.PubMed/NCBI
23	Hwang HS and Kim HA: Chondrocyte apoptosis in the pathogenesis of osteoarthritis. Int J Mol Sci. 16:26035–26054. 2015. View Article : Google Scholar : PubMed/NCBI
24	Lee HG and Yang JH: PCB126 induces apoptosis of chondrocytes via ROS-dependent pathways. Osteoarthritis Cartilage. 20:1179–1185. 2012. View Article : Google Scholar : PubMed/NCBI
25	Ito K and Shinomura T: Development and application of a new Silent reporter system to quantitate the activity of enhancer elements in the type II collagen gene. Gene. 585:13–21. 2016. View Article : Google Scholar : PubMed/NCBI
26	Motomura H, Seki S, Shiozawa S, Aikawa Y, Nogami M and Kimura T: A selective c-Fos/AP-1 inhibitor prevents cartilage destruction and subsequent osteophyte formation. Biochem Biophys Res Commun. 497:756–761. 2018. View Article : Google Scholar : PubMed/NCBI
27	Stancker TG, Vieira SS, Serra AJ, do Nascimento Lima R, Dos Santos Feliciano R, Silva JA Jr, Dos Santos SA, Dos Santos Vieira MA, Simões MCB, Leal-Junior EC, et al: Can photobiomodulation associated with implantation of mesenchymal adipose-derived stem cells attenuate the expression of MMPs and decrease degradation of type II collagen in an experimental model of osteoarthritis. Lasers Med Sci. 33:1073–1084. 2018. View Article : Google Scholar : PubMed/NCBI
28	Pohlig F, Guell F, Lenze U, Lenze FW, Mühlhofer HM, Schauwecker J, Toepfer A, Mayer-Kuckuk P, von Eisenhart-Rothe R, Burgkart R and Salzmann GM: Hyaluronic acid suppresses the expression of metalloproteinases in osteoarthritic cartilage stimulated simultaneously by interleukin 1β and mechanical load. PLoS One. 11:e01500202016. View Article : Google Scholar
29	Li WQ, Dehnade F and Zafarullah M: Oncostatin M-induced matrix metalloproteinase and tissue inhibitor of metalloproteinase-3 genes expression in chondrocytes requires Janus kinase/STAT signaling pathway. J Immunol. 166:3491–3498. 2001. View Article : Google Scholar : PubMed/NCBI