Biomedical Engineering Reference
In-Depth Information
preliminary model, the experimental and computational investigations support each
other mutually in the deeper understanding of the investigated problem. Finally, the
model can also participate in the further design of the effective drug delivery
therapies.
Considering the overview in Chapter 1 , the objective of modeling is to describe
the essential transport and transformation mechanisms associated with the drug
(or gene) delivery from the external phase to the various targets (in cytoplasm,
nucleus or mitochondria). Also, exocytosis of the nanoparticle components is con-
sidered, e.g. a recirculation of the undelivered drug (or gene) components.
Accordingly, our model has to describe the following processes:
Fluid phase macropinocytosis (FPM) is a low efficiency, nonspecific process
that involves the bulk uptake of solutes in exact proportion to their concentration
in the extracellular fluid;
In nonspecific adsorptive endocytosis (NAE) the molecules are bound to the cell
surface and concentrated before internalization, i.e. the molecules interact pref-
erentially with generic complementary binding sites, such as lectin or charged
surface elements;
Receptor mediated endocytosis (RME) also involves concentration of the mole-
cules, with certain ligands bound to receptors on the cell surface and becoming
concentrated before internalization. The cytoplasm membrane folds inward to
form coated pits, such as clathrin-coated pits. These inward budding vesicles
bud to form cytoplasmic vesicles;
Lipid rafts mediated endocytosis (LRME) is another kind of specific endocytosis,
where the transport is supported by special lipids of the membrane channels;
Exocytosis of the nanovehicles is enhanced by the motor proteins.
In the following model, nonspecific NAE will be taken into consideration in
nonspecific FPM (called FPM/NAE).
2.2
Compartments and Components
In the cellular compartmentalization of nanoparticles, the specific role of the
so-called early and late endosomes, and lysosomes have to be taken into consider-
ation. These specific subsystems of the cell are involved in the trafficking and
degradation of the receptor mediated components.
The cellular compartments with estimated percentages are the followings
(Alberts et al. 2002 , see Table 12-1, p. 661; note, this composition is reported for
hepatocytes): cytosol (cyt): 54%; plasma membrane (pm): 0.5% (ER function in
endo/exocytosis is not considered in this paper); mitochondria (mit): 22%; nucleus
(nuc): 6%; early endosomes (ee): 1%; late endosomes (le): 1%; and lysosomes
(lys): 1%. The capacity of the external phase is taken into account by an external/
cytoplasm ratio of approximately 1:1.
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