Chemistry Reference
In-Depth Information
headgroups are mono- or multivalent structures with a nonionic or ionic
character depending on the type of interactions targeted to membrane
lectin and proteoglycans. The hydrophobic domains represent the non-
polar hydrocarbon moieties of glycolipids and are usually made of two
types of hydrophobic moieties, aliphatic chains or steroid domain.
Glycotargeting eciencies and physical properties of glycoliposomes can
be affected by structural variations in the hydrophobic domain such as
length, specific type of chemical bonds (ester or ether bonds), and
relative position of the hydrocarbon chains.
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The aliphatic chains of
glycolipids used in liposomal vectors are linear or branched, saturated or
mono-unsaturated, generally ranging from C14:0 to C18:0 or C18:1. In
the steroid groups, cholesterol is by far the most frequently encountered
and used as an alternative to aliphatic chains because of its rigidity, as
well as its endogenous biodegradability and fusion activity. The spacer-
arms include various hydrophobic or hydrophilic groups (alkyl groups,
peptides and poly(ethylene glycol) PEG) with different lengths and flexi-
bility. These linkers between hydrophilic and hydrophobic domains can
exert a tremendous effect on the degree of carbohydrate ligand exposure
at the vesicle surfaces.
This chapter aims to cover recent developments of glycolipids in the
field of nanocarriers, with a special focus on site-specific and ligand-
directed drug and gene delivery, and vaccine adjuvant applications.
2 Glycolipid-based drug delivery nanosystems
In this section, representative examples of glycoliposomes used as active
targeting drug delivery systems, will be introduced according to the na-
ture of the targeted cells and the lectins they express on their surface.
2.1 Dendritic cell glycotargeting
Dendritic cells (DCs) are unique antigen-presenting cells (APCs) which
play a critical role in the regulation of the adaptive immune response
against pathogens or tumor cells. Depending on their location, DCs have
morphologic and functional differences. Immature DCs found in per-
ipheral tissues are highly phagocytic towards exogenous antigens, which
are subsequently processed and presented on the cell surface along with
appropriate co-stimulation molecules. Following a maturation process,
these cells move into the blood or lymph and then circulate to various
lymphoid organs where they present antigens to T-cells in conjunction
with major histocompatibility complex (MHC) molecules for recognition
by the T-cell receptor. DCs are receiving increasing scientific and clinical
interest due to their key role in anti-cancer host responses and potential
use as biological adjuvants in tumor vaccines, as well as their involve-
ment in the immunobiology of tolerance and autoimmunity. In par-
ticular, the binding of formulations bearing specific antigens to DCs by
active targeting represents a promising strategy for enhancing vaccine
ecacy. The targeting not only requires high specificity for receptors that
abundantly express on DCs surfaces, but also the ability to be rapidly
internalized and loaded into compartments that contain elements of
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