| Popis: |
The application of endogenous-like particles for the targeting of drugs to specific sites in the body is advantageous because endogenous transport vehicles do not trigger immunological reactions, are completely biodegradable, and escape recognition by the reticuloendothelial system (stealth behaviour). In the present study a lipid emulsion is prepared that mimics lipoprotein particles (so-called chylomicrons), which transport dietary lipids into the liver. Commercially available lipids were mixed with recombinant human apolipoprotein (apo) E, and a hydrophobized antiviral drug (dioleoyl iododeoxyuridine) was incorporated. Emulsions had a mean size of 82 nm, acquired about 70 molecules of apo E, and incorporated up to 130 prodrug molecules per particle. Incorporation of the drug into recombinant chylomicrons resulted in a 40-fold increased liver uptake and a markedly reduced extrahepatic deposition as compared to the free drug. An intracellular drug concentration of 700 nM can be achieved within liver parenchymal cells offering an effective drug concentration for the treatment of viral liver diseases, i.e. hepatitis B. |
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