Liposomes hepatitis

Liposomes are phospholipid vesicles that have been evaluated both as adjuvants and as vehicles for antigens and adjuvants (17). A liposomal hepatitis A (Hep A) vaccine (virosomes) has been extensively evaluated in the clinic and is currently licensed for a Hep A vaccine (18). Alternative adjuvants that have been used in a few products include L-tyrosine (allergy vaccine) and MPL (cancer treatment). The various adjuvants (mainly alum salts) used in vaccine formulations and their quantities per dose are listed in Table 1. 

Preclinical Results Obtained with Particles. Poly-L-lysine and poly-L-Ornithine were used to generate particles that can entrap pDNA. The cationic polymers can be coupled to a targeting molecule such as galactose or mannose for enhanced delivery to the liver after intravenous or intraportal injections in mice [102-104]. Expression in other organs than the liver (for example, kidneys) is observed however, expression in the liver using these particles is dominant. Such particles are found to be more efficient and to persist for a longer time in the circulation than liposomes. Hepatic expression of the pDNA delivered by poly-L-Lysine particles can be found several months after delivery [105]. These promising formulations were not evaluated in humans. 

Roerdink, F., Dijkstra, J., Hartman, G., Bolscher, B., and Scher-phof, G. L. (1981). The involvement of parenchymal, Kupffer and endothelial liver cells in the hepatic uptake of intravenously injected liposomes, Biochim. Biophys. Acta, 677, 79-89. 

Gregoriadis, G., and Neerunjun, D.E., Control of the rate of hepatic uptake and catabolism of liposome-entrapped proteins injected into rats possible therapeutic applications, European Journal of Biochemistry, 1974, 47, 179-185. 

Harashima H, Sakata K, Funato K, et al. Enhanced hepatic uptake of liposomes through complement activation depending on the size of liposomes. Pharm Res 1994 11 402. 

Engler OB, et al. A liposomal peptide vaccine inducing CD8(- -) T cells in HLA-A2.1 transgenic mice, which recognise human cells encoding hepatitis C virus (HCV) proteins. Vaccine 2004 23 58. 

Immunopotentiating reconstituted influenza virosomes (IRTV) are spherical 150-nm sized particles consisting of a phospholipid bilayer in which influenza virus A/Singapore strain-derived hemagglutinin (HA) and neuraminidase (NA) are intercalated. As such, they resemble and mimic the influenza virus envelope. The difference from conventional liposome formulations lies in the inclusion of the viral envelope proteins HA and NA as well as viral phospholipids. Especially, the inclusion of influenza virus HA provides IRIV with delivery and immimogenic capacities. IRTV are licensed for human use as adjuvant in hepatitis A vaccination and as influenza subunit vaccine (1). 

Recently a new liposome-based hepatitis A vaccine (Epaxat), developed by the... 

Both lipoprotein lipase and the less well understood hepatic lipase are related structurally to pancreatic lipase.42,4213 In addition to hydrolysis of the triacylglycerols, the uptake of materials from lipoproteins probably involves shedding of intact phospholipids, perhaps as liposome-like particles 40... 

Kim, Ch.K., Jeong, E.J. Development of dried liposomes as effective immuno-adjuvants for hepatitis B surface antigen. bit./. Pharm. 115,193-199,1995... 

The high hydrophilicity and corresponding low lipophilicity of both EDTA and DTP A result in very low uptake of these chelating agents into cells. In an endeavour to increase intracellular uptake of DTPA, Rahman et al.98 injected liposomally entrapped DTP A into mice which had hepatic accumulations of 239Pu. Although this was an effective treatment for mice it proved to be unsatisfactory for hamsters99. ... 

J. A. A. M. Kamps, H. W. M. Morselt, P. J. Swart, D. K. F. Meijer, and G. L. Scherphof, Massive targeting of liposomes, surface-modified with anionized albumins, to hepatic endothelial cells, Proc. Natl. Acad. Sci. USA 94 11681-11685, (1997). 

Asialofetuin is an asialoglycoprotein containing terminal galactosyl residues that have been used to target liposomes to the liver. There was seven-fold enhancement in CAT expression in the liver when succinylatcd asialofetuin was added to preformed plasmid/ DOTAP Chol complexes to provide a ligand for hepatic asialoglycoprotein receptor. 

Figure 14.6 Inhibitory effects of poly anions on the hepatic uptake of 32P-labeled plasmid/cationic liposome complexes administered intravenously into mice at 1 minute after DNA iv injection of excess poly anions. Hepatic accumulation was determined at 10 minute post-injection. Key (orange) free plasmid, (pale orange) 1 5 w/w plasmid/LipofectACE, (blue) 1 5 w/w plasmid/LipofectACE. Reproduced with permission from Physicochemical and pharmacokinetic characteristics of DNA/cationic liposome complexes, Mahato R.I. et al. (1995) J. Pharm. Sci., 84 1267-1271...

Daunorabicin (DaunoXome, Gilead Sciences, Inc.) Doxorubicin (Doxil/Caelyx, Ortho Biotech ProductsLP/Sequus Pharmaceuticals) Amphotericin B (Ambisome/Abelcet, Fujisawa Healthcare, Wyeth Pharmaceuticals) Doxorubicin (Myocet/Evacet, Sopherion/ Liposome Company) Hepatitis A virus envelope proteins (Epaxal, Berna Biotech) Influenza virus (Inflexal V, Berna Biotech) Verteporfin (Visudyne, Novartis Ophthalmics) Kaposi s sarcoma Kaposi s sarcoma Fungal infections in immunocompromised patients Metastatic breast cancer Hepatitis A Influenza Age-related macular degeneration... 

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