Biomedical Engineering Reference
In-Depth Information
(a)
(b)
White pulp
Red pulp
Circulation:
Closed
Trabeclua
Open
Sinusoid diameter: 20-30 μm
Blood flow: 150 mL/min
(c)
C
1
2
3
Sinusoid
Open circulation
Closed circulation
4
1
2
Reticular fibers
3
Neutrophils
Macrophages
4
Red blood cells
FIGURE 14.5
Structure of the spleen. (a) The spleen parenchyma is protected by a fibrous capsule and is
composed of the white and red pulp. (b) From the trabecular circulation, the arteries empty into the splenic
sinusoids (closed circulation) or directly into the parenchyma (open circulation). (c) Reticular fibers confer a
highly tortuous architecture to the red pulp, and blood components must squeeze through the 200-nm wide
fenestration of the sinusoids.
sequestration in the spleen (Demoy et al. 1999; Liu et al. 2008; Cho et al. 2009a). Sufficiently flex-
ible particles can be stored in the spleen upon initial sieving and, if they avoid phagocytosis, are
gradually released into the bloodstream within a few days (Merkel et al. 2011). Further develop-
ments and understandings of this strategy are needed to evaluate its potential for the delivery of
active compounds.
14.4.2 aBc p
heNoMeNoN
Preclinical pharmacokinetic and biodistribution studies generally involve the administration of a
single dose of CDCs. However, experiments have revealed that the blood clearance of a second CDC
dose highly increases after an initial sensitization. This phenomenon, referred to as the accelerated
blood clearance (ABC) effect, has been observed for various CDCs (e.g., liposomes) (Laverman
et al. 2001), lipid complexes (Tagami et al. 2009), and polymeric nanoparticles (Ishihara et al. 2009).
The ABC effect is divided into two phases, initial sensitization (induction) and effectuation. During
induction, direct CDC interactions with B cells in the spleen induce the secretion of antibodies
(Ishihara et al. 2009; Judge et al. 2006). Within 2-4 days of the first injection, the antibody titer in
blood increases and the effectuation phase begins. CDCs injected during this period are opsonised
by circulating antibodies and rapidly cleared by the liver. The blood circulation times of subsequent
