الفهرس 
Utility of nanocarriers for targeted delivery of an antiviral drug to the liver
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Abstract
Daclatasvir is a new direct-acting antiviral agent NS5A inhibitor used for oral treatment of hepatitis C viral infection. The NS5A replication complex is a necessary component of HCV replication since it assists in the replication of RNA and assembly of the virus and supplies an appropriate environment for viral growth. Based on previous clinical trials and pharmacokinetic parameters the accumulation of Daclatasvir in the active tissue (liver) is much lower than its accumulation in plasma. Thus, appropriate dosage forms need to be prepared to enhance liver delivery and lower other tissue distribution in an attempt to lower side effects. Many lipid-based vesicles such as liposomes have been investigated as a colloidal carrier for oral drug delivery systems. However, their low stability in the gastrointestinal tract is still a major issue. The second biological barrier for nanocarriers to reach blood is their ability to pass through the gut epithelia. Nanocarriers must adhere to the mucus or possess facilitated diffusion through it leading to transenterocytic vesicular internalization. The third biological barrier is blood protein adsorptions on nanocarriers’ surface ”opsonization” inducing their uptake by mononuclear phagocyte system and excretion. For effective delivery to hepatocytes, circulating vesicles should have smaller diameter than liver sinusoidal fenestrations (up to 150-200 nm), for ease extravasation into the space of Disse. Also, nanocarriers have to be capable for cell internalization through endocytic mechanisms.The cellular uptake into hepatocytes is mediated through ligand endocytosis or membrane fusion