capillary cluster which receives its blood flow from an afferent arteriole. Unlike
other capillary beds, glomerulus drains into an efferent arteriole rather than a
venule. The high resistance of an efferent arteriole results in a high pressure within
the glomerulus. The high blood pressure inside the glomerulus is the driving force
for water and solute to be filtered out of blood and into the space of Bowman’s
capsule. Bowman’s capsule surrounds the glomerulus and collects filtered fluid and
solutes from blood in the glomerulus. Glomerulus consists of three layers, which
are endothelium, basement membrane and epithelium (podocyte). Endothelial cells
have numerous, relatively large pores (fenestrae) with a diameter of 70–90 nm.
While basement membrane prevents filtration of plasma proteins with 2–8 nm-sized
holes and consists of laminins, type IV collagen, agrin and nidogen. Epithelium
consists of podocytes which are attached to the basement membrane by their foot
processes with 4–11 nm-sized slits. This layer is the final filtration barrier of plasma
proteins before the fluid enters the Bowman’s capsule. Additionally, negatively
charged foot processes limit the filtration of negatively charged substances, such as
albumin. As a result, only low molecular weight molecules (<30,000 Dalton) are
filtered out of blood in the glomerulus (Fig. 19.2) [2].
Bowman’s capsule is the starting point of the renal tubules. Filtered fluid runs
through renal tubule and enters into collecting duct system. In the proximal tubule,
weak electrolyte drugs are actively secreted, and water is reabsorbed. In the loop of
Henle, water reabsorption occurs. Also, passive reabsorption of water and lipophilic
drugs takes place in the distal tubules. In the collecting duct system, the concentration of the urine can be adjusted by action of antidiuretic hormone. Urine depart
the medullary collecting ducts and go through the renal papilla, calyces, pelvis, and
finally into the bladder via the ureter.
19.2.2 Renal Excretion of Nanomaterials
Nanomaterials with hydrodynamic diameters (HD) <6 nm are filtered in the
glomerulus and thus can be excreted in urine. Generally, nanoparticles (NP) with
HD >8 nm are not filtered with some exceptions which will be discussed in the last
part of this section. In case of NPs with the intermediate size of 6–8 nm, the charge
of the NPs determine the filtration and positively charged NPs are prone to be
filtered more because of negatively charged foot process. Once NPs cleared out
from blood at renal corpuscle, the majority of the NPs are excreted via urine
because nanomaterials are generally not reabsorbed at proximal/distal tubules.
Rapid renal excretion of NPs is a huge advantage in their biocompatibility, and
thus renal clearable nanoprobes were developed using multiple types of NP platforms including quantum dots (QD), C dots (or Cornell dots), and ultrasmall gold
NPs [3] (Table 19.1). In 2007, renal clearable QDs were developed (Fig. 19.3a) [4],
and other inorganic NPs followed including ultrasmall fluorescent silica NPs such
as C dots [11, 12, 17], glutathione-coated gold NPs [6, 18] and carbon nanotubes
[15]. Ultra-small dye encapsulated fluorescence silica NPs, also known as C dots
19 Excretion and Clearance
349
other capillary beds, glomerulus drains into an efferent arteriole rather than a
venule. The high resistance of an efferent arteriole results in a high pressure within
the glomerulus. The high blood pressure inside the glomerulus is the driving force
for water and solute to be filtered out of blood and into the space of Bowman’s
capsule. Bowman’s capsule surrounds the glomerulus and collects filtered fluid and
solutes from blood in the glomerulus. Glomerulus consists of three layers, which
are endothelium, basement membrane and epithelium (podocyte). Endothelial cells
have numerous, relatively large pores (fenestrae) with a diameter of 70–90 nm.
While basement membrane prevents filtration of plasma proteins with 2–8 nm-sized
holes and consists of laminins, type IV collagen, agrin and nidogen. Epithelium
consists of podocytes which are attached to the basement membrane by their foot
processes with 4–11 nm-sized slits. This layer is the final filtration barrier of plasma
proteins before the fluid enters the Bowman’s capsule. Additionally, negatively
charged foot processes limit the filtration of negatively charged substances, such as
albumin. As a result, only low molecular weight molecules (<30,000 Dalton) are
filtered out of blood in the glomerulus (Fig. 19.2) [2].
Bowman’s capsule is the starting point of the renal tubules. Filtered fluid runs
through renal tubule and enters into collecting duct system. In the proximal tubule,
weak electrolyte drugs are actively secreted, and water is reabsorbed. In the loop of
Henle, water reabsorption occurs. Also, passive reabsorption of water and lipophilic
drugs takes place in the distal tubules. In the collecting duct system, the concentration of the urine can be adjusted by action of antidiuretic hormone. Urine depart
the medullary collecting ducts and go through the renal papilla, calyces, pelvis, and
finally into the bladder via the ureter.
19.2.2 Renal Excretion of Nanomaterials
Nanomaterials with hydrodynamic diameters (HD) <6 nm are filtered in the
glomerulus and thus can be excreted in urine. Generally, nanoparticles (NP) with
HD >8 nm are not filtered with some exceptions which will be discussed in the last
part of this section. In case of NPs with the intermediate size of 6–8 nm, the charge
of the NPs determine the filtration and positively charged NPs are prone to be
filtered more because of negatively charged foot process. Once NPs cleared out
from blood at renal corpuscle, the majority of the NPs are excreted via urine
because nanomaterials are generally not reabsorbed at proximal/distal tubules.
Rapid renal excretion of NPs is a huge advantage in their biocompatibility, and
thus renal clearable nanoprobes were developed using multiple types of NP platforms including quantum dots (QD), C dots (or Cornell dots), and ultrasmall gold
NPs [3] (Table 19.1). In 2007, renal clearable QDs were developed (Fig. 19.3a) [4],
and other inorganic NPs followed including ultrasmall fluorescent silica NPs such
as C dots [11, 12, 17], glutathione-coated gold NPs [6, 18] and carbon nanotubes
[15]. Ultra-small dye encapsulated fluorescence silica NPs, also known as C dots
19 Excretion and Clearance
349