NUTRACEUTICAL FORMULATIONS CONTAINING GLUCOSAMINE AND CHONDROITIN SULPHATE IN THE TREATMENT OF OSTEOARTHRITIS: EMPHASIS ON CLINICAL EFFICACY AND FORMULATION CHALLENGES
DOI:
https://doi.org/10.22159/ijcpr.2017v9i2.17380Keywords:
Osteoarthritis, Glucosamine, Chondroitin, Clinical use, Formulation technologiesAbstract
Osteoarthritis (OA) is essentially a debilitating disease symptomatized by a gradual loss of articular joint cartilage, causing painful impairment among the population of different ages, particularly patients over the age of 50 y. Nutraceuticals; namely glucosamine and chondroitin have been widely used in the treatment of OA. The chondroprotective properties of the aforementioned agents have been reported, allowing the repair and recovery of the articular surface in OA. The purpose of this review article is to report the current evidence for the use of glucosamine and chondroitin sulphate in the treatment of knee OA with emphasis on their indications for clinical use, effectiveness and safety. It also highlights the role of some advanced formulation technologies in optimizing the delivery of those drugs.
Keywords: Osteoarthritis, Glucosamine, Chondroitin, Clinical use, Formulation technologies
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References
Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum 2012;64:697–707.
Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM, et al. Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med 2000;133:635-46.
Bae DK, Yoon KH, Song SJ. Cartilage healing after microfracture in osteoarthritis knees. Arthroscopy 2006;22:367-74.
Felson DT. The epidemiology of osteoarthritis: prevalence and risk factors. In: Kuettner KE, Goldberg VM. editors. Osteoarthritic disorders. Rosemont, IL: American Academy of Orthopedic Surgeons; 1995. p. 13-24.
Felson DT. An update on the pathogenesis and epidemiology of osteoarthritis. Radiol Clin North Am 2004;42:1-9.
Martin JA, Buckwalter JA. Roles of articular cartilage aging and chondrocyte senescence in the pathogenesis of osteoarthritis. Iowa Orthopaedic J 2001;21:1-7.
Balazs EA. Viscoelastic properties of hyaluronic acid and biological lubrication. Univ Mich Med Cent J 1968;9:255-9.
Balazs EA. The physical properties of synovial fluid and the special role of hyaluronic acid. In: Helfet A. editor. Disorders of the knee. 2nd ed. Philadelphia: JB Lippincott; 1982. p. 61-74.
Bradley E, Des Meules M. Arthritis in Canada: an ongoing challenge. Ottawa: Health Canada; 2003;2:7-34.
Conaghan PG. Osteoarthritis in 2012: parallel evolution of OA phenotypes and therapies. Nat Rev Rheumatol 2013;9:68–70.
Towheed THE. Published meta-analyses of pharmacological therapies for osteoarthritis. Osteoarthritis Cartilage 2002;10:836-7.
Towheed TE, Hochberg MC. A systematic review of randomized controlled trial of pharmacological therapy in osteoarthritis of the knee, with an emphasis on trial methodology. Semin Arthritis Rheum 1997;26:755-70.
Garner SE, Fidan D, Frankish RR, Judd M, Shea B, Towheed T, et al. Celecoxib for rheumatoid arthritis. Cochrane Database Systematic Rev 2002;(4):CD003831.
Lorza C, Altman R. Chondrotection in osteoarthritis. Bull Rheum Dis 1997;46:5-7.
Theodosakis J, Adderly B, Fox B. The Arthritis Cure. New York, NY: St Martin's Press; 1997.
Henrotin Y, Mobasheri A, Marty M. What is the current status of chondroitin sulfate and glucosamine for the treatment of knee osteoarthritis? Maturitas 2014;78:184–7.
Toffoletto O, Tavares A, Casarini DE, Redublo BM, Ribeiro AB. Farmacocinetica da associacao de glucosamine e sulfato de condroitina em humanos sadios do sexo masculino. Acta Ortop Bras 2005;13:235-7.
Laverty S, Sandy JD, Celeste C, Vachon P, Marier JF, Plaas AHK. Synovial fluid levels and serum pharmacokinetics in a large animal model following treatment with oral glucosamine at clinically relevant doses. Arthritis Rheum 2005;52:181-91.
Adebowale A, Du J, Liang Z, Leslie JL, Eddington ND. The bioavailability and pharmacokinetics of glucosamine hydrochloride and low molecular weight chondroitin sulfate after single and multiple doses to beagle dogs. Biopharm Drug Dispos 2002;23:217-25.
Setnikar I, Giachetti C, Zanolo G. Absorption, distribution and excretion of radioactivity after a single intravenous or oral administration of [14C] glucosamine to the rat. Pharmatherapeutica 1984;3:538-50.
Setnikar I, Giacchetti C, Zanolo G. Pharmacokinetics of glucosamine in the dog and in man. Arzneimittelforschung 1986;36:729-35.
Setnikar I, Palumbo R, Canali S, Zanolo G. Pharmacokinetics of glucosamine in man. Arzneimittelforschung 1993;43:1109-13.
Aghazadeh-Habashi A, Sattari A, Pasutto FM, Jamali F. Single dose pharmacokinetics and bioavailability of glucosamine in the rat. J Pharm Sci 2002;5:181-4.
Persiani S, Roda E, Rovati LC, Locatelli M, Giacovelli G, Roda A. Glucosamine oral bioavailability and plasma pharmacokinetics after increasing doses of crystalline glucosamine sulfate in man. Osteoarthritis Cartilage 2005;13:1041-9.
Bayliss MT, Osborne D, Woodhouse S, Davidson C. Sulfation of chondroitin sulfate in human articular cartilage. The effect of age, topographical position, and zone of cartilage on tissue composition. J Biol Chem 1999;274:15892-900.
Burkhardt D, Michel BA, Baici A, Kissling R, Theiler R. Comparison of chondroitin sulphate composition of femoral head articular cartilage from patients with femoral neck fractures and osteoarthritis and controls. Rheumatol Int 1995;14:235-41.
Clegg DO, Reda DJ, Harris CL, Klein MA, O'Dell JR, Hooper MM, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med 2006;354:795-808.
Jackson CG, Plaas AH, Sandy JD, Hua C, Kim-Rolands S, Barnhill JG, et al. The human pharmacokinetics of oral ingestion of glucosamine and chondroitin sulfate taken separately or in combination. Osteoarthritis Cartilage 2010;18:297-302.
Simánek V1, Kren V, Ulrichová J, Gallo J. The efficacy of glucosamine and chondroitin sulfate in the treatment of osteoarthritis: are these saccharides drugs or nutraceuticals? Biomed Pap Med Fac Univ Palacky Olomounc Czech Repub 2005;149:51-6.
Kelly GS. The role of glucosamine sulfate and chondroitin sulfate in the treatment of degenerative joint disease. Alternative Med Rev 1998;3:27-39.
McAlindon TE, LaValley MP, Felson DT. Efficacy of glucosamine and chondroitin for treatment of osteoarthritis. JAMA 2000;284:1241-2.
Reginster JY, Deroisy R, Rovati LC, Lee RL, Lejeune E, Bruyere O, Giacovelli G, et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 2001;357:251-6.
Pavelká K, Gatterová J, Olejarová M, Machacek S, Giacovelli G, Rovati LC. Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med 2002;162:2113-23.
Towheed TE, Maxwell L, Anastassiades TP, Shea B, Houpt J, Robinson V, Hochberg MC, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev 2005;2:CD002946.
Sawitzke AD, Shi H, Finco MF, Dunlop DD, Harris CL, Singer NG, et al. Clinical efficacy and safety of glucosamine, chondroitin sulphate, their combination, celecoxib or placebo was taken to treat osteoarthritis of the knee: 2-year results from GAIT. Ann Rheum Dis 2010;69:1459–64.
Müller-Fassbender H, Bach GL, Haase W, Rovati LC, Setnikar I. Glucosamine compared to ibuprofen in osteoarthritis of the knee. Osteoarthritis Cartilage 1994;2:61-9.
Noack W, Fischer M, Förster KK, Rovati LC, Setnikar I. Glucosamine sulfate in osteoarthritis of the knee. Osteoarthritis Cartilage 1994;2:51-9.
Reichelt A, Forster KK, Fischer M, Rovati LC, Setnikar I. Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the knee. A randomised, placebo-controlled, double-blind study. Arzneimittelforschung 1994;44:75-80.
Hughes R, Carr A. A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee. Rheumatology (Oxford) 2002;41:279-84.
Bruyere O, Honore A, Ethgen O, Rovati LC, Giacovelli G, Henrotin YE, et al. Correlation between radiographic severity of knee osteoarthritis and future disease progression. Results from a 3-year prospective, placebo-controlled study evaluating the effect of glucosamine sulfate. Osteoarthritis Cartilage 2003;11:1-5.
Cibere J, Kopec JA, Thorne A, Singer J, Canvin J, Robinson DB, et al. Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis. Arthritis Rheum 2004;51:738-45.
Bruyere O, Pavelka K, Rovati LC, Deroisy R, Olejarova M, Gatterova J, et al. Glucosamine sulphate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: Evidence from two 3 y studies. Menopause 2004;11:138-43.
Herrero-Beaumont G, Ivorra JA, Del Carmen Trabada M, Blanco FJ, Benito P, MartÃn-Mola E, et al. Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator. Arthritis Rheum 2007;56:555-67.
Houpt JB, McMillan R, Wein C, Paget-Dellio SD. Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee. J Rheumatol 1999;26:2423-30.
McAlindon TE, Formica M, LaValley M, Lehmer M, Kabbara K. Effectiveness of glucosamine for symptoms of knee osteoarthritis: results from an internet-based randomized double-blind controlled trial. Am J Med 2004;117:643-9.
Hochberg MC, Clegg DO. Potential effects of chondroitin sulfate on joint swelling: a GAIT report. Osteoarthritis Cartilage 2008;16(Suppl 3):22-4.
Reichenbach S, Sterchi R, Scherer M, Trelle S, Bürgi E, Bürgi U, et al. Meta-analysis: chondroitin for osteoarthritis of the knee or hip. Ann Intern Med 2007;146:580-90.
Kahan A, Uebelhart D, De Vathaire F, Delmas PD, Reginster JY. Long-term effects of chondroitins 4 and 6 sulfate on knee osteoarthritis: the study on osteoarthritis progression prevention, a two-year, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2009;60:524-33.
Messier SP, Mihalko S, Loeser RF, Legault C, Jolla J, Pfruender J, et al. Glucosamine/chondroitin combined with exercise for the treatment of knee osteoarthritis: a preliminary study. Osteoarthritis Cartilage 2007;15:1256-66.
Rai J. Efficacy of chondroitin sulfate and glucosamine sulfate in the progression of symptomatic knee osteoarthritis: a randomized, placebo-controlled, double-blind study. Bull Postgrad Inst Med Educ Res Chandigarh 2004;38:18-22.
Bucsi L, Poór G. Efficacy and tolerability of oral chondroitin sulfate as a symptomatic slow-acting drug for osteoarthritis (SYSADOA) in the treatment of knee osteoarthritis. Osteoarthritis Cartilage 1998;6:31-6.
Bourgeois P, Chales G, Dehais J, Delcambre B, Kuntz JL, Rozenberg S. Efficacy and tolerability of chondroitin sulphate 1200 mg/day vs chondroitin sulfate 3 X 400 mg/day vs placebo. Osteoarthritis Cartilage 1998;6(Suppl A):25-30.
Conrozier T. Anti-arthrosis treatments: efficacy and tolerance of chondroitin sulfates (CS 4 and 6). Presse Med 1998;27:1862-5.
Mazieres B, Combe B, Phan Van A, Tondut J, Grynfeltt M. Chondroitin sulfate in osteoarthritis of the knee: a prospective, double-blind, placebo-controlled multicenter clinical study. J Rheumatol 2001;28:173-81.
Mathieu P. Radiological progression of internal femorotibial osteoarthritis in gonarthrosis. Chondroprotective effect of chondroitin sulfates ACS4-ACS6. Presse Med 2002;31:1386-90.
Uebelhart D, Malaise M, Marcolongo R, de Vathaire F, Piperno M, Mailleux E, et al. Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: A one-year, randomized, double-blind, multicenter study versus placebo. Osteoarthritis Cartilage 2004;12:269-76.
Michel BA, Stucki G, Frey D, de Vathaire F, Vignon E, Bruehlmann P, et al. Chondroitins 4 and 6 sulfate in osteoarthritis of the knee: a randomized, controlled trial. Arthritis Rheum 2005;52:779-86.
Mazieres B, Hucher M, Zaim M, Garnero P. Effect of chondroitin sulfate in symptomatic knee osteoarthritis: a multicentre, randomised, double-blind, placebo-controlled study. Ann Rheum Dis 2007;66:639-45.
Alekseeva LI, Chichasova NV, Benevolenskaia LI, Nasonov EL, Mendel’ OI. Combined medication ARTRA in the treatment of osteoarthrosis. Ter Arkh 2005;77:69-75.
Junginger HE. Excipients as absorption enhancers. In: Krishna R, Yu L. EdsZ. Biopharmaceutics applications in drug development. Springer, New York, USA; 2007;74:139-74.
Persiani S, Roda E, Rovati LC, Locatelli M, Giacovelli G, Roda A. Glucosamine oral bioavailability and plasma pharmacokinetics after increasing doses of crystalline glucosamine sulfate in man. Osteoarthr Cartil 2005;13,1041–9.
Qian S, Zhang Q, Wang Y, Lee B, Betageri GV, Chow MSS, Huang M, Zuo Z. Bioavailability enhancement of glucosamine hydrochloride by chitosan. Int J Pharm (Amsterdam, Neth) 2013;455:365-73.
Thanou M, Verhoef JC, Junginger HE. Oral drug absorption enhancement by chitosan and its derivatives. Adv Drug Delivery 2001;52:117–26.
Piai JF, Lopes LC, Fajardo AR, Rubira AF, Muniz EC. Kinetic study of chondroitin sulphate release from chondroitin Sulphate/Chitosan complex hydrogel. J Mol Liq 2010;156:28-32.
Anisha BS, Sankar D, Mohandas A, Chennazhi KP, Nair SV, Jayakumar R. Chitosan-hyaluronan/nano chondroitin sulfate ternary composite sponges for medical use. Carbohydr Polym 2013;92:1470-6.
Park SN, Lee HJ, Lee KH, Suh H. Biological characterization of the EDC-crosslinked collagen-hyaluronic acid matrix in dermal tissue restoration. Biomaterials 2003;24:1631-41.
Yeh MK, Cheng KM, Hu CS, Huang YC, Young JJ. Novel protein-loaded chondroitin sulfate-chitosan nanoparticles: preparation and characterization. Acta Biomater 2011;7:3804–12.
Collins MN, Birkinshaw C. Morphology of cross-linked hyaluronic acid porous hydrogels. J Appl Polym Sci 2011;120:1040-9.
Sharma A, Arora S. Dermal delivery of glucosamine sulphate: formulation, characterization and performance evaluation. World J Pharm Pharm Sci 2013;2:6448-62.
Craciunescu O, Gaspar A, Trif M, Moisei M, Oancea A, Moldovan L, et al. Preparation and characterization of a collagen-liposome-chondroitin sulphate matrix with potential application for inflammatory disorders treatment. J Nanomater; 2014. http://dx.doi.org/10.1155/2014/903691
Yannas IV, Tzeranis DS, Harley BA, So PT. Biologically active collagen-based scaffolds: advances in processing and characterization. Philos Trans R Soc A 2010;368:2123–39.
Mozafari MR. Nanoliposomes: preparation and analysis. Methods Mol Biol 2010;605:29–50.
Cuppoletti J. Ed. Nanocomposites and Polymers with Analytical Methods. InTech, Rijeka, Croatia; 2011. p. 1.
Umerska A, Corrigana OI, Tajbera L. Design of chondroitin sulfate-based polyelectrolyte nanoplexes: formation of nanocarriers with chitosan and a case study of salmon calcitonin. Carbohydrate Polymers 2017;156:276–84.
Da Silva GT, Voss GT, Kaplum V, Nakamura CV, Wilhelm EA, Luchese C, et al. Development, characterization and biocompatibility of chondroitin sulfate/poly(vinyl alcohol)/ bovine bone powder porous biocomposite. Mater Sci Eng C 2017;72:526-36.
United States Commitee on Health, Education, Labor and Pensions, Subcommittee on Aging. Centre of DiseaseControls role in combating the burden of arthritis. Washington: Department of Health and Human Services; 2004.
Jordan KM, Arden NK, Doherty M, Bannwarth B, Bijlsma JW, Dieppe P, et al. Standing committee for international clinical studies including therapeutic trials escisit. eular recommendations 2003:an evidence-based approach to the management of knee osteoarthritis: report of a task force of the standing committee for international clinical studies including therapeutics trials (ESCISIT). Ann Rheum Dis 2003;62:1145-55.
Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, et al. American college of rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip and knee. Athrtitis Care Res (Hoboken) 2012;64:465-74.
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