Cross-Linked Gelatin Microcapsules for Drug Delivery in a Arthritic TMJ

Abstract

A majority of individuals reporting temporomandibular joint (TMJ) disorders have joint damage, inflammation or arthritis (Manfredini, Chiappe & Bosco, 2006; Plesh, Sinisi, Crawford & Gansky, 2005). The joint will show loss of extra-cellular matrix components in the articular cartilage and subchondral bone resulting in destruction of cartilage and bone, such processes lead to inflammation and exacerbation of joint tissue catabolism (Tanaka, Detamore & Mercuri, 2008). Matrix metalloproteinases 1 and 9 (MMP-1 and MMP-9) are two major enzymes that contribute to tissue catabolism and have been observed in patients with TMJ disorders (Kanyama, Kuboki, Kojima, Fujisawa, Hattori, Takigawa & Yamashita, 2000; Srinivas, Sorsa, Tjaderhane, Niemi, Raustia, Pernu, Teronen & Salo, 2001; Yoshida, Takatsuka, Hatada, Nakamura, Tanaka, Ueki, Nakagawa, Okada, Yamamoto & Fukuda, 2006). Reversal of these disease processes and treatment of the joint to reduce pain are effective in the early stages of the disease, but treatment often fails to alleviate the severe, chronic pain caused by advanced joint degeneration (Gerwin, Hops & Lucke, 2006; Tanaka, Detamore & Mercuri, 2008). Treatment of TMJ osteoarthritis with intra-articular injections of non-steroidal antiinflammatory drugs (NSAIDs) and opiates into the superior joint space have shown efficacy (Bryant, Harrison, Hopper & Harris, 1999; Swift, Roszkowski, Alton & Hargreaves, 1998; Zuniga, Ibanez & Kozacko, 2007). Intra-articular administration versus systemic administration of NSAID or opiates would be advantageous for treatment of TMJ inflammation and pain because local administration avoids the ectopic effects seen with NSAIDs like rofecoxib (i.e., Vioxx) (Lin, Weisdorf, Solovey & Hebbel, 2000) or opiates. For example, nonselective NSAIDS can cause intestinal bleeding, whereas some selective cyclooxygenase-2 inhibitors have significant cardiovascular and renal safety risks (Davies & Jamali, 2004; Mukherjee, Nissen & Topol, 2001). Moreover, opioids frequently cause constipation, sedation, nausea, vomiting, and respiratory depression (Mercadante, 1999). Intra-articular injection remains controversial in light of decades of mixed reports demonstrating intra-articular injections either accelerate or trigger destruction of tissues within the TMJ and the surrounding area (Bjornland, Rorvik, Haanaes & Teige, 1994; Sugisaki, Ikai & Tanabe, 1995; Westesson, Eriksson & Liedberg, 1986). Recent reports