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Abstract The increasing number of biomedical uses for Hyaluronic acid(HA) has encouraged the development of a broad range of HA-based derivatives with enhanced or modulated properties. HA has been the subject or many previous reviews focusing on its biological functions and medical applications and drug delivery (Gaffny et al., 2010). Hyaluronan (also cald Hyaluronic acid or Hyaluronate) is a nonsulfated glucosaminoglycan distributed widely through connective, epithelial, and neural tissues. It is one of the chief components of the extracellular matrix, significantly to cell proliferation and migration, and may also be involved in the progression of some malignant tumors and it is believed to play a role in virulence (Stern et al., 2004) and (Saravanakumar et al., 2010)). Chronic Hepatitis C Virus A long term hepatitis C infection more than 6 months. Hepatitis C is liver inflammation caused by HCV virus. The hepatitis C virus replicates at a rapid rate. As consequence, it has a high degree of genetic diversity, which allows it to escape effective surveillance by the host’s humoral and cellular immune response ( Houghton et al., 2009). Liver cirrhosis results from necrosis of the liver cells follwed by fibrosis and nodule formation. In liver cirrhosis, there is an increase in extracellular matrix (ECM) components, activation of cells producing matrix materials, the (ECM) comprises hyaluronic acid, collagenous and non-collagenous proteins (Leminin, Proteoglucans and Elastin), which are all similar qualitatively but different quantitatively from those in normal liver (Klingberg and White., 2013). Both the synthesis and deposition of these components increase during fibrogenesis , These components and their split products are released into the systemic Introduction 2 circulation, leading to an increase in their serum concentration and these have been investigated as potential markers of the fibrotic process quantitatively (Schiavon et al., 2008). Hyaluronic acid (HA) is a high molecular weight polysaccharide produced mainly by fibroblasts and other specialized connective tissue cells. Although widely distributed through out the body, part of HA enters the general circulation via the lymphatic system and is rapidly cleared and degraded mainly in liver, the blood capillaries in the liver are distinctly wavy, their walls are lined by sinusoidal endothelial cells (SEC), Kupffer and hepatic stellate cells. SEC are uniquely adapted to perform important filtration function due to small fenestration or sieve plate that contain high specific HA receptor. In normal liver this receptor maintains physiological level of HA by capturing and degrading it through the enzymatic action of hyaluronidase, while, in fibrotic liver SEC show impairing in there capacity to clear HA, resulting in both relative and absolute elevation of serum HA level ( Gaof et al., 2008) and (Casterol., 2012). Function of hyaluronic acid Conjugation of HA with drugs containing amino group may provide a potential drug delivery system facilitating specific drug delivery to long active effect (Ulbrich et al., 2005) and (Kim., 2012). Through the modification of HA, it can reversibly bind multiple molecules of drug per molecule of polymer. This polymer–drug conjugates can be administrated as prodrugs to give a sustained release of the active drug over time. Advantages thereof include a decrease in toxicity effects of the free drug, the particular polymer and molecular weight thereof can be selected to suit the particular application of which producing new drug application are of particular interest (Bouhadir et al., 2007). |