Liver drug targeting

CA C1 C01.033 Cathepsin L-like peptidase (Fasciola sp.) Potential drug target for liver fluke infection... 

The use of LDL and other lipoproteins in drug targeting has been reviewed [170,172], Damle et al. [173] have shown that radiopharmaceuticals, such as iopanoic acid, a cholecystographic agent, could be incorporated in chylomicron remnants by esterification with cholesterol and used for liver imaging. About 87% of the chylomicron remnant-loaded iopanoic acid accumulated in the liver within 0.5 hour after administration, compared with 31% accumulated using a... 

The treatment of tumours in the liver with drug targeting preparations is hampered by the lack of tumour specifity of most preparations. Liposomes incorporating the immunomodula-tor muramyl tripeptide phosphatidylethanolamine have been used as an aspecific approach to increasing the number of tumouricidal macrophages in the liver in order to prevent the development of metastases [99].To date, the greatest tumour cell specificity has been obtained... 

The viability and function tests described above are used to evaluate the hepatocytes within the slice. Up to now, tests to measure the viability of the non-parenchymal cells have not been reported. The presence of the latter cell types is one of the conceptual advantages of slices as compared to isolated hepatocytes. As some drug targeting devices are designed to target non-parenchymal cells in the liver, the development of tests for the sinusoidal cell types deserves more attention. For example, the uptake of substrates such as succinylated human serum albumin (Suc-HSA,which is specifically endocytosed by endothelial cells [79]), or hyaluronic acid [80], can be used to assess the functionality of endocytotic pathways in the endothelial cells in the liver [81]. Other modified proteins that are specifically taken up by Kupffer cells such as mannosylated HSA, may be used to assess the functionality of the endocytotic pathway in Kupffer cells [79]. Another parameter which can be used to assess the functionality of these non-parenchymal liver cells, is the excretion of cytokines in response to pro-inflammatory stimuli. Non-parench5mal cell function in liver slices will be described in more detail in the Section 12.7. 

In contrast to isolated hepatocytes, liver slices retain the cellular architecture of the Uver without prior digestion with collagenase. This makes a systematic comparison of the data relating to transport of free drugs as well as drug targeting moieties from isolated hepatocytes and liver slices, an attractive model for studying the potential and limitations of the liver slice model in this area of research. 

Efficacy Testing of the Drug Targeting Device in the Liver... 

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