Biomedical Engineering Reference
In-Depth Information
surface groups may be engineered to increase the cellular uptake or tissue accumulation
[38, 39]. The size of particles is critical for the effectiveness of many therapeutic agents
during delivery to the brain due to the blood brain barrier. Research has shown that par-
ticles with a diameter of less than 64 nm can move though the brain, while larger diameter
(114 nm) particles densely coated with polyethylene glycol can diffuse within the brain
[40]. Polymeric nanoparticles are able to be functionalized with biological molecules that
accumulate in tumors while bypassing healthy cells [41]. Farokhzad
et al
. investigated clin-
ically nanoparticles with targeting molecules that recognize an antigen expressed on the
surface of most prostate tumor cells [42]. Although, much research has been conducted on
the concept of targeted delivery, few formulations reached clinical trials due to the poten-
tial risks of conjugation challenges, such as finding the appropriate ligand receptor. In
addition, some cancer cells, including cancer stem cells, do not show any upregulation in
specific receptors [43].
Tumor cells can be specifically identified by monoclonal antibodies and lysed by tumor-
killing substances without harming normal cells. For example, FDA approved Cetuximab
for use in squamous cell carcinoma and colorectal carcinoma [44]. Conjugation of peptide
sequences, such as arginine-glycine-aspartate (RGD), to the nanostructures has been pro-
posed previously. For example, it was reported that a poly(
d
,
l
-lactide-co-glycolic) (PLGA)
nanoparticle conjugated with RGD can be used to deliver therapeutic agents at
inflammatory sites expressing the upregulated intercellular cell-adhesion molecule-1 [45].
In another study, RGD conjugated to the poly(amidoamine) dendrimers was utilized for
gene delivery into mesenchymal stem cells (MSCs) [46]. These oligopeptides, as well as
extracellular matrix (ECM) molecules can directly regulate stem-cell functions through
the interaction between integrins on the cell surface and ligands on the ECM molecules [47].
Other small molecules like retinoic acid or fluoxetin can be utilized for gene expression
modulation [48, 49].
Ceramic Nanostructures
Targeted drug delivery by ceramic nanoparticles has drawn special attention during
recent years. The porous structure of ceramic materials at the nanoscale size, stability of
their size at body temperature or pH, and also nonswelling behavior in aqueous media
are the main characteristics of these structures [50]. In addition, biocompatibility, alter-
ation in their surface-charge density, and functionality by changing their stoichiometry,
make them suitable for both drug and growth factor delivery [51]. Moreover, surface
functionalization of ceramic-based particles can be easily utilized for conjugation of
biomolecules to target specific ligands [52]. Prasad
et al
. synthesized silica-based
nanoparticles with different functional groups, such as hydroxyl, thiol, amine, and car-
boxyl [53]. Entrapment of a water-insoluble anticancer drug in silica [54, 55], ibuprofen
release from alumina [56], valproic acid delivery to the brain by titania [57], and insulin
delivery by a calcium phosphate dehydrate core [58], are examples of investigated
ceramic-based structures for controlled release. Hui
et al
. [59] evaluated the ability of
silica, hydroxyapatite, and zirconia nanoparticles as gene delivery vehicles. Adair
et al
.
[60, 61] developed colloidally stable calcium phosphate nanoparticles for hydrophobic
antineoplastic and fluorescence agent delivery. In other research [62], doxorubicin was
loaded on PEGylated silica nanoparticles. Titania nanotubes were also suggested for
delivery of different drugs such as albumin, sirolimus, or paclitaxel [63]. The release rate
of drugs can be controlled by alteration of nanotube geometry, including diameter,
length, and wall thickness [64].
