الفهرس 
Chemical structure and Physicochemical propertiesOnly 14 pages are availabe for public view
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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).