Arthritis is a joint disorder that is caused by inflammation of one or more joints. It has been estimated that the total cost of the arthritis bill for the United States is over $50 billion dollars annually [Corti, M. C. et al. Exp. Res. (2003)15:359-363]. Among many types of arthritis (e.g., over 100 identified), osteoarthritis (OA) is the most common type with a prevalence exceeding 20 million in the United States. Id. The cause of OA is generally related to wear and tear of the cartilage on the surfaces, while another common type of arthritis, rheumatoid arthritis, is typically caused by the inflammation resulting from an overactive immune system. The treatment of arthritis is dependent on the precise type of arthritis.
Current treatment of OA mainly focuses on joint mobilization, which is enabled by avoiding overloading as well as control of pain and inflammation using medications administered systemically or intra-articularly [Grainger, R. and Cicuttini, F. M. Med. J. Aust. (2004)180:232-236]. Lubricant molecules that separate opposing surfaces can reduce friction under the pressure and, therefore, supplementation of biolubricants in synovial fluid (SF) is a reasonable option for treatment of OA [Abate, M. and Pelotti, P., J. Med. Sci. (2008)113:261-278].
Several different substances have been proposed as the native boundary biolubricants. Hyaluronic acid (HA) and the glycoprotein lubricin are the two main components in SF. HA is a polymer of D-glucuronic acid and D-N-acetylglucosamine, which degrades under inflammatory conditions such as in OA. Clinical application of HA (so called viscosupplementation), however, did not demonstrate the efficacy of HA in treating OA [Benz, M. and Chen, N. J. Biomed. Mater. Res., Part A (2004) 71:6-15]. On the other hand, lubricin is generally composed of ˜44% proteins, ˜45% carbohydrates, and ˜11% surface active phospholipids (SAPL), of which ˜41% are phosphatidylcholines (PCs), ˜27% phosphatidylethanolamines (PEs), and ˜32% sphingomyelins [Swann, D. A. et al. Arthritis Rheum. (1981) 24:22-30; Swann, D. A. and Mintz, G. Biochem. J. (1979) 179:465-471; Swann, D. A. et al. J. Biol. Chem. (1981) 256:5921-5925; Schwarz, I. M. and Hills, B. A. Br. J. Rheumatol. (1998) 37:21-26; Sarma, A. V. et al. J. Orthoped. Res. (2001)19:671-676]. The SAPL in SF has been previously reported to facilitate low friction in articulating cartilage. For example, injection of the SAPL 1,2-dipalmitoylphosphtidylcholine (DPPC) into human OA joints that are SAPL deficient was reported to result in mobility improvement lasting up to 14 weeks without major side effects [Vecchio, P. and Thomas, R.; Hills, B. A. Rheumatology (1999) 38:1020-1021; Oloyede, A. et al. Clin. Biomech. (2004) 19:534-542]. A previous report on globular lipid vesicles localized in the thick upper surface layer of healthy cartilage indicates their role in lubrication [Watanabe, M. et al. Med. Electron Microsc. (2000) 33; 16-24]. DPPC liposomes combined with high molecular weight HA (˜2000 kDa) had shown better lubricating ability than HA alone in animal models [Kawano, T. et al. Arthritis Rheum. (2003) 48:1923-1929]. Recently, size and composition effect of different liposomes on joint lubrication has been compared using an ex-vivo model [Sivan, S. et al. Langmuir (2010) 26:1107-1116]. Although the role of SAPL in joint lubrication has been reported, clinical applications of these SAPL molecules still remain challenging. This is partly because SAPL has low molecular weight and does not have stable and robust material properties to sustain the therapeutic effect. Therefore, there is still a need to develop a clinically viable and effective formulation for treatment of joint disorders such as OA.