Biomedical Engineering Reference
In-Depth Information
concentration, and production parameters such as temperature
122
achieving as
long as 5-7weeks. The formulation can be modulated for prolonged release
without any burst or with different percentages of burst followed by prolonged
release.
67
The burst can be used to deliver an initial dose when desired.
5.8 NM CLEARANCE
Concerns about NM clearance after drug delivery are prevalent because the
technology is still in its infancy. Thus, it is very important to understand how
the human body clears NMs that are used in NP-based drug delivery.
49,123
After
the body has distributed oxygen, nutrients, and systemically administered NM-
mediated drugs via the vascular and lymphatic systems, it has to clear anything
and everything that is introduced. I.v. introduced materials are scavenged and
cleared from the circulation by Kupffer cells and macrophages.
10
Clearance
is facilitated by surface deposition of blood opsonic factors and complement
proteins on the injected drug-NP. Studies have recently been published on the
detailed information regarding the phagocytosis and clearance of carbon nano-
tubes in vitro.
124,125
The size and surface properties of the injected NMs affect
both clearance and opsonization. Bigger particles that are 200 nm or greater in
diameter activate the complement system more efficiently and are cleared faster
from the circulatory system than the smaller particles in poorly studied and
less understood biological mechanisms. However, the biological mechanism of
particle clearance is likely related to the basic geometry and surface characteris-
tics (charge, functional groups, shape, etc.) of particles that mediate binding of
blood proteins and opsonins.
10,11
Theoretically, NMs may be engineered to introduce various characteristics
that are designed to suit the phenotype, physiological activity, and recognition
mechanisms of specific subpopulations of macrophages to enhance differential
opsonization and clearance.
126
On the other hand, NMs less than 100nm have
been associated with variable levels of toxicity through different mechanisms.
In a study by Nel et al.,
127
inhaled particles can elicit pulmonary inflammation
and oxidative stress and disrupt distal organ function. As NMs decrease in size,
their relative surface area in air is increased, causing an enhanced exposure to
several proposed toxic mechanisms including HIs, redox cycling, and free radi-
cal formation. In this manner, a 20-nm particle would have roughly 100 times
the inherent toxicity of a 2-µm particle in an equivalent dose based on mass,
assuming a direct relationship with surface area.
The surface chemistry and design of NMs impacts the pharmacokinetic
profile of a given drug it carries by altering its aggregation in the body.
49,123
Although NMs including dendrimers, QDs, and micelles are prone to aggrega-
tion, this can be circumvented by surface engineering. NMs such as QDs can
be made water soluble, dispersible, and stable in serum by coating their sur-
face with polydentate phosphine or hydrophilic polymers.
128,129,130
NMs can be
coated with polymers such as PEG
10,126
that suppress macrophage recognition
