Plasmatic circulating factor H adsorbed on bacteria or the surfac

Plasmatic circulating www.selleckchem.com/products/MDV3100.html factor H adsorbed on bacteria or the surface of colloidal systems physiologically

inhibits their complement-mediated destruction. This result is ascribable to factor H action as cofactor for the inactivation of the complement C3b factor and the alternative pathway convertase [55]. Therefore, factor H behaves as a dysopsonin. Surolia and Bachhawat demonstrated that liposomes coated with sialic acid derivatives are poorly recognised by the macrophages as they mimic the mammalian cell surface [56]. Stealth nanocarriers have been obtained using a variety of polysialic acid derivatives, Inhibitors,research,lifescience,medical including gangliosides [57–61], ganglioside derivatives, and glycophorin [62–64]. On the contrary, the coating with orosomucoid protein, a sialic acid rich protein, did not yield stealth poly(isobutylcyanoacrylate) nanoparticles. This effect was ascribed to the poor density of the sialic acid on the particle surface that does not allow for proper coating or to the inefficient conformation of the clustered glycans [65]. The liposome coating with the monosialoganglioside Inhibitors,research,lifescience,medical GM1 (Figure 2), a brain-tissue-derived monosialoganglioside, was found to inhibit the alternative complement pathway by promoting the association of factor H to C3b factor on the vesicle surface [66]. In mice, the liposome decoration with 5–7mol% of

GM1 was found to increase the vesicle stability and inhibit the complement activation Inhibitors,research,lifescience,medical cascade, which resulted in prolonged permanence in the circulation [67]. As the molar ratio of GM1 in liposomes increases, the macrophage uptake inhibition increases up to 90% with 10mol% GM1 [64]. Figure 2 first Chemical structure of the monosialoganglioside GM1. Few studies postulated that the shielding of the negative charges of GM1 by the bulky, neutral hydrophilic Inhibitors,research,lifescience,medical sugar moieties is paramount to its stealth activity Inhibitors,research,lifescience,medical [58]. Nevertheless, other

investigations showed that macromolecules bearing unshielded negative charges, namely, the ganglioside GM3, a sialic acid synthetic derivative, and a GM1 semisynthetic compound, increase the blood circulation time of sub-200nm liposomes in mice [63]. Therefore, it can be concluded that the sterical organization of the ganglioside residues is primarily responsible for preventing the opsonisation of liposome containing glycolipids. Interestingly, GSK-3 studies performed with mice and rats showed that the gangliosides have a specie-specific activity. Indeed, the GM1 decoration was effective in mice while it did not have any beneficial effect on the circulation time of liposomes in rats [63]. 2.2.5. Zwitterionic Polymers Zwitterionic phospholipid derivatives have been demonstrated to reduce the complement activation induced by liposomes [68]. Based on this evidence, synthetic zwitterionic polymers have been used to produce stealth drug delivery systems. These materials bind water molecules more strongly than polymers forming hydrogen bridges such as PEG.

Leave a Reply

Your email address will not be published. Required fields are marked *

*

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>