Biomedical Engineering Reference
In-Depth Information
Nanoparticles should possess appropriate physical dimensions and surface
characteristics. Thus, although there is
in vitro
evidence of activation of human
macrophages with particles as large as 90 mm, the size amenable to phagocytosis
is 1-10 mm, with an optimum of 3 mm (Hirota et al.
2007
). Similarly, the surface
characteristics are important for both phagocytosis and macrophage activation.
Phagocytosis of particles made up of poly(styrene), an extremely hydrophobic
material, is less efficient than that of PLGA particles of equivalent size and shape
but of lower hydrophobicity. However, extremely hydrophobic biodegradable poly-
mer, high molecular weight PLA nanoparticles, still report efficient phagocytosis
(Misra et al.
2010
; Muttil et al.
2007
; Sharma et al.
2001
). This may be due to the
fact that their formulations contain an unusually high drug payload, which could
modify the surface characteristics of the particles by virtue of high surface density
of drug molecules. It was demonstrated the advantage of particles with an elliptical
geometry for macrophage uptake (Hickey et al.
1996
). However, surface and shape
can also affect lung deposition of inhaled therapies (Misra et al.
2010
). A stringent
aerosol particle size requirement represents another important challenge. The delivery
efficiency of many traditional aerosol formulations is low due to the fact that a
large fraction of the particles have aerosol sizes that are too large (>~5 mm), and are
thus retained in the mouth and throat to reach in the digestive tract rather than
lungs. In contrast, aerosol particles that are too small (<0.4 mm, which is within the
range of typical polymeric nanoparticles described in the literature) are also
expected to have very low deposition efficiency (Rogueda and Traini
2007
). The
'fine particle fraction', defined as % particulate matter below a threshold size, can
be used to predict lung deposition (Hickey et al.
1996
). In the airways, the humidity
is very high, at almost 100%. Therefore, the drug carrier has to resist wetting and
subsequent aggregation in the respiratory tract. It can thus be appreciated that the
twin objectives of lung deposition and macrophage targeting will depend strongly
on size, shape and surface properties of drug carrier systems. Particles with an
aerodynamic diameter between 1 and 5 mm are deposited in the lower lungs, with
larger particles remaining in the throat and smaller particles being exhaled (Cryan
et al.
2007
).
Medication using DPI can result in high local levels of drug in epithelial lining
fluid of the airways and lower respiratory tract. Drugs administered topically to the
lungs, via aerosol are attractive in that they achieve higher levels in the lungs with
fewer systemic side effects.
There are several issues associated with the delivery of polymeric nanoparticles
to the lungs. Biocompatibility and clearance are two very important considerations
(Davis et al.
2008
).
Biodistribution and Therapeutic Efficacy of Inhaled/Instilled Liposomes
Upon pulmonary administration, liposomes are preferentially taken up by alveolar
macrophages instead of type I or II alveolar cells. This was determined in an
experiment where small (161 nm) and large (1,455 nm) liposomes (DPPC: DPPG:
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