Tissue-Targeting Ability of Saccharide-Poly(L-Lysine) Conjugates.

Abstract

To evaluate the effect of introducing a saccharide moiety to poly(amino acids) on tissue distribution, several glycoconjugates of epsilon-(2-methoxyethoxyacetyl)-poly(L-lysine) of three molecular weights were synthesized using an octylene spacer between the sugar and polymer chain. Methoxyethoxyacetylation of the epsilon-amino group of the lysine unit in poly(L-lysine) was useful for avoiding nonspecific distribution to many tissues as the result of cationic charges. The tissue-targeting ability of each saccharide moiety was considered as the actual amount changed in each tissue caused by saccharide modification. Galactose terminated saccharides such as galactose, lactose and N-acetylgalactosamine accumulated exclusively in the liver, probably by the hepatic receptor. These conjugates could therefore be good carriers for a drug delivery system to the liver. On the other hand, the mannosyl and fucosyl conjugates were preferentially delivered to the reticuloendothelial systems such as those in the liver, spleen and bone marrow. In particular, fucosyl conjugates accumulated more in the bone marrow than in the spleen. Xylosyl conjugates accumulated mostly in the liver and lung. Generally, the accumulated amount in the target tissue increased with increasing molecular weight and an increased number of saccharides on one molecule of polymer.

Galactosylated chitosan/DNA nanoparticles prepared using water-soluble chitosan as a gene carrier

“…2). The sugar moieties of glycoproteins play an important role in tissue distribution to the targeted organ in the body [34]. To achieve specific targeting to hepatocytes using ASGP-R, the optimal density of galactose should be conjugated with gene carriers [11,35].…”

Lipid, Sugar and Liposaccharide Based Delivery Systems

“…for drugs include poly-L-glutamic acid [33], poly-L-lysine [34], polyacrylamide [35] and carboxymethyl-dextran [32].…”

Biocompatibility of Synthetic and Bio-Material Fusion

“…Materials like lipids, natural and synthetic polymers, carbohydrates, surfactants and dendrimers are used as drug carriers [1][2][3] . The drug conjugate can be designed for improving its potential for complex - interactions towards the target moiety and drug [4][5][6][7] . Biological materials are eco-friendly, but they have limitation with regard to the proposed application as they are less durable in terms of mechanical strength and resistance to corrosion.…”

“…(ii) Ligands with weak to intermediate field strength and multidenticities may be suitable to design pharmaceutically acceptable metal carriers with embedded metal centres. To make hexamine cobalt [Co(NH 3 ) 6 ] + biocompatible, the four NH 3 ligands are replaced by ligands such as N 2 O 4 or its isoelectronic moieties 17 . Furthermore, ligands with chiral centres can optimally tune the activity of metal centres towards their catalytic application in a living system 18 ; and with some exceptions, aromaticity reduces cytotoxicity 19 .…”

“…Syntheticbiological fusion can be used to design target-oriented drug delivery systems [4][5][6][7] (Table 2) by selecting appropriate -cloud extension, such as estrogen moieties for targeting the breast, or xylylbicyclam, a potent anti-HIV agent that mobilizes stem cells (AMD3100, 'Mozobil') via targeting the 7-helix membrane receptor, CXCR4. Specific metallomacrocycle configurations can be recognized by proteins via metal coordination to specific amino acid side chains, H-bonding and hydrophobic interactions, allowing drug design optimization 25 .…”