Targeted Drug Delivery - Nanomaterials for Medical Applications - page 180

Over the past few years, NMs have been studied as drug delivery sys-
tems called NM drug carriers or simply nanocarriers. Enormous focus is
being directed toward developing NMs for drug delivery for controlling
the release of drugs, stabilizing labile molecules (e.g. proteins, peptides, or
DNA) from degradation, and site-specific drug targeting. 1 The late 1969s
and early 1979s saw the advent of polyacrylamide micelle polymerization 2
along with other polymers. 2 , 3 , 4 There are already a number of nano-enabled
drugs that are sold in the market. 5 This generation of nano-enabled drugs is
mainly dependent on the small size of the particles to increase the surface
area to enhance the bioavailability of poorly soluble drugs and to improve
the structure of the particles for delayed release. In the United States, a
few of the nano-enabled drugs include Rapamune ® /Pfizer, Emend ® /Merck,
INVEGA ® SUSTENNA ® /Janssen, all based on Elan's NanoCrystal ® tech-
nology, Abraxane ® /Abraxis Bioscience, and Triglide™/Sciele Pharma. 6 In
these drugs, the NPs introduced improved functionalities that include diag-
nosis, targeting, drug delivery, and enhanced transport and uptake proper-
ties. This chapter is dedicated to the various aspects of different NMs for
targeted drug delivery.
5.2 NANOMATERIALS AS VEHICLES FOR DRUG DELIVERY
Nanomaterials possess qualities that allow for efficient drug delivery. The
nanometer size of NMs allows for extravasation through the endothelium in
inflammatory sites, tumors, epithelium (e.g. intestinal tract and liver), or pen-
etrate microcapillaries. 1 Their sizes allow for efficient uptake by various cell
types which, when used for drug delivery leads to selective drug accumulation
at target sites. 7 , 8 , 9 Earlier studies have demonstrated that nanoparticles (NPs)
are more suited for intravenous (i.v.) delivery than microparticles (>1 µm) as a
drug delivery system. 9 Because the smallest capillaries in the body are 5-6 µm
in diameter, the size of particles being distributed into the bloodstream must be
significantly smaller than 5 µm, without forming aggregates, to ensure that the
particles do not cause an embolism. 1 Colloidal NMs that vary in size from 10 to
200 nm 2 have been extensively studied for drug delivery but particles >200 nm
are not heavily pursued.
When NMs are injected into the blood stream, extensive interactions with
plasma proteins, cells, and other blood components take place as reviewed by
Moghimi et al. 10 Liposomes are one example of NMs as drug carriers where
such interactions have been studied in detail. Phospholipids in the outer bilayer
of liposomes attract some known opsonins such as immunoglobulins and com-
plement 11 and other plasma components such as lipoproteins. 12 The reticulo-
endothelial macrophages that reside in the liver and spleen have been shown to
involve these events during clearance of liposomes.
As liposomes and other NMs accumulate in the liver and spleen, the mecha-
nism could be related to the nature of proteins that adsorb onto the surface
of systemically administered NMs. 13 Studies have shown that in the plasma,