Macrophages are prospective targets for therapeutic agents containing carbohydrates due to the presence of C-type lectins. Targeting of macrophage mannose receptors for drug delivery is being paid more and more attention. Creative Biolabs has organized a staff of outstanding scientists who have engaged in mannosylated liposome design and development for many years. We are glad to serve our global clients with professionalism and expertise in this field.
Macrophage receptors are located in the cytoplasmic membrane and recognize carbohydrates of microbial origin, which are often related to post-translational modification of proteins. These receptor molecules contain one or several carbohydrate recognition domains and are classified into three groups. Mannose receptors, including CD 206 and DEC-205 are type I transmembrane proteins containing several carbohydrate recognition domains. Mannose receptors are expressed by most macrophages, the highest expression level being inherent in the hepatic endothelial cells, renal mesangial cells, smooth muscle cells and eye retina pigment epithelial cells. The expression of mannose receptors is stimulated by vitamin D and interleukin (IL) 4, IL10 and IL13, and suppressed by interferon-gamma (INFG) and tumor necrosis factor-alpha (TNFa). The extracellular part of the receptor, which is responsible for binding to mannose residues, consists of a short NH2-terminal cysteine-rich domain, fibronectin II repeat, and a C-type lectin-like domain. The spatial arrangement of the carbohydrate recognition domains in receptor molecules is very important. The linear arrangement of carbohydrate recognition domains in the polypeptide chain of the mannose receptor is convenient for the recognition of the terminal mannose molecules. The carbohydrate recognition domains of the DC-SIGN tetramer have a higher affinity to mannose residues in branched structures with a small distance between mannose residues. The trimers of mannose-binding lectin molecules combined into hexamers are suitable for binding ligands with a high density of mannose residues.
Fig.1 Fabrication of mannosylated polyanhydride (Gantrez AN) nanoparticles by the reaction of mannose derivative with the copolymer before the nanoparticles' formation (A), or direct coating of the just-formed nanoparticles (B). (Irache, 2008)
Some interesting studies are associated with the use of mannosylated liposomes for the delivery of therapeutic agents. Efficient targeted drug delivery to macrophages has been considered of high interest for the treatment of many intracellular parasitic infections, such as leishmaniasis. In the therapy of leishmaniasis induced by Leishmania parasite within macrophages, toxicity and drug resistance are major obstacles. In this context, the antileishmanial property of a benzyl derivative of the antibiotic MT81 (Bz2MT81) was tested in mannose-coated liposomes against visceral leishmaniasis in hamsters. This formulation eliminated intracellular amastigotes of L. donovani within splenic macrophages more efficiently than control liposomes or free Bz2MT81. Moreover, in similar work, the leishmanicidal property of piperine loaded in mannose-coated liposomes was tested in experimental visceral leishmaniasis in hamsters. Mannose-coated liposomal-containing piperine can eliminate intracellular amastigotes of L. donovani in splenic macrophages much more efficiently. Furthermore, in a similar animal model, mannosylated liposomes containing andrographolide were found to be more potent in reducing the parasitic burden in the spleen as well as in reducing hepatic and renal toxicity.
Studies have shown that mannose residues have the highest receptor affinity for macrophage mannose receptors. Moreover, mannose is an inexpensive and readily accessible reagent. Thus, active targeting of macrophage mannose receptors can be considered as an efficient strategy for the design of targeted delivery systems. With an experienced team of experts in the development of Macrophage-targeted Liposome Drug Delivery Systems, Creative Biolabs has accumulated rich experience in mannosylated liposome design and development. The enhancement of the uptake of mannosylated liposomes by macrophages is an important factor, and inhibition experiments can be performed to confirm the regulation of the interaction of macrophage mannose receptors with mannosylated liposomes via the receptor-mediated endocytosis. For more detailed information, please feel free to contact us or send us your inquiry or question.
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