Biomedical Engineering Reference
In-Depth Information
Sub-micron
emulsion
Solid drug
nanoparticle
Liposome
Lipid-core
micelle
Dendrimer
Polymeric
micelle
Polymeric
nanoparticle
PEG 'corona'
PEGylated phospholipid
for PK modification
immunoactive
targeting group
immunoliposome
targeting group
Typical size
range
5-10 nm
50-500 nm
100-150 nm
50-200 nm
PEG
Albumin
Poorly water-soluble
drug eg. paclitaxel
Water-soluble drug
eg. doxorubic in HCl
Lipid-based surfactant
eg. glycocholic acid
Polymeric surfactant
eg. PEG-b-PLA
Oil core
eg. vitamin E
Phospholipid
Targeting group
eg. folate
Biodegradable
polymer eg. PLGA
Fig. 1
Various commonly used nanostructures in drug delivery
removal of the particle from plasma within only minutes to a few hours, thus limiting
the therapeutic usefulness of the nano-drug formulation where extended circulation
time is important for performance. This chapter is therefore dedicated to explaining
the reticuloendothelial system, its functions, pathophysiology and mechanisms of
nanomedicine removal and detailing ways in which uptake via the system can either
be avoided or promoted.
2
Pathophysiology of the Reticuloendothelial System
The reticuloendothelial system (commonly referred to as the RES) is comprised of
a collection of organs (Fig.
2
) that contain high proportions of the cells that make
up the body's defence system against particulate pathogens. Specifically, it is a col-
lection of monophagocytic cells that are largely manufactured by the bone marrow
and transported throughout the body to aid in the removal of foreign organisms,
damaged cells and products of cellular degradation. Immature macrophages in the
systemic circulation are monocytes that migrate into tissues once matured. Mature,
tissue fixed macrophages make up the Kupffer cells in the liver and the reticular
cells in the spleen, lungs, lymph nodes and bone marrow. These cells remove for-
eign material via rapid phagocytosis. In some instances, initial priming via lympho-
cytes and the internalization of material into endosomes is required. The endosomes
eventually fuse with lysosomes that release enzymes into the endosome that digest
the engulfed material. For material that is resistant to degradation via lysosomal
enzymes, the material remains trapped within the macrophage until the cell eventu-
ally dies. The largest concentration of macrophages in the body are located in the
liver and lungs, however macrophages in different locations exhibit very different
biochemical and functional activity that can influence their ability to scavenge
various nanomedicines.
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