Biomedical Engineering Reference
In-Depth Information
6.3.4 O
THER
N
ANOSTRUCTURES
6.3.4.1 Dendrimers
Dendrimers are highly branched, globular macromolecules with many arms emanating from a
central core and are emerging as a new class of polymeric nanosystems with applications in drug
delivery. The stepwise synthesis of dendrimers affords molecules with a highly regular branching
pattern, a unique molecular weight or low polydispersity index, and a well-defi ned number of
peripheral groups [53-55]. The distinctive star-shaped architecture of dendrimers has contributed
to increased interest in their application as drug molecules due to the loading potential in the
interior or on the surface [39].
Drug molecules can be associated with dendrimers by physical encapsulation in the void spaces
of the interior by incubation, forming a drug network, or prodrugs can be formed from a covalent or
noncovalent linkage to the dendrimer surface [23].
Dendrimers are being investigated for drug and gene delivery, as carriers for penicillin, and for
use in anticancer therapy. Dendrimers used in drug delivery studies typically incorporate one or
more of the following polymers: polyamidoamine (PAMAM), poly(l-glutamic acid) (PG), polyeth-
yleneimine (PEI), poly(propylene imine), and PEG [56].
A comparison of the features of dendrimers with those of linear polymers shows that the
dendritic architecture can provide several advantages for drug delivery applications. For example,
the controlled multivalency of dendrimers can be used to attach several drug molecules, target-
ing groups, and solubilizing groups to the periphery of the dendrimers in a well-defi ned manner.
Dendrimer toxicity and immunogenicity should be considered when it is applied for drug delivery.
Partial derivatization of the dendrimer surface, such as, a PAMAM dendrimer conjugated with
PEG or fatty acids, helps to signifi cantly reduce toxicity and immunogenicity due to a reduction or
shielding of the positively charged dendrimer surface [23,57,58]. In addition, the low polydispersity
of dendrimers can provide reproducible pharmacokinetics compared with that of some linear
polymers, which can have vastly different molecular weights within a given sample [53,54]. Recent
progress has been made in the application of biocompatible dendrimers to cancer treatment, includ-
ing their use as drug delivery systems for anticancer agents such as cisplatin and doxorubicin and as
agents for both boron neutron capture therapy and photodynamic therapy (PDT) [53].
PDT is a promising approach for the treatment of malignant tumors and macular degradation.
PDT involves the systemic administration of photosensitizers, followed by the local application
of a laser with a specifi c wavelength to the diseased sites. Upon photoirradiation, photosensitizers
generate highly reactive singlet oxygen (
1
O
2
), thereby inducing light-induced cytotoxicity
(photocytotoxicity). In PDT, the development of delivery systems for photosensitizers has recently
received much attention to improve the selectivity and effectiveness of PDT as well as prevent the side
effects such as skin hypersensitivity [27]. Nishiyama et al. developed an ionic dendritic porphyrin,
as potential photosensitizers for PDT, in which the focal core of the porphyrin is surrounded by
the third generation of poly(benzyl ether) dendrons with peripheral ionic carboxyl groups. The
dendritic framework of the dendritic porphyrins is assumed to sterically prevent the interaction (i.e.,
self-quenching) of the center porphyrins, ensuring the effective singlet oxygen production from the
dendritic porphyrins even at extremely high concentrations [59].
6.3.4.2 MagneticNanoparticles
Magnetic nanoparticles can be composed of iron oxide, magnetite, or nickel, cobalt, or neodymium-
iron boron oxides. These particles are magnetic or superparamagnetic and range in diameter
between 10 and 200 nm. Magnetite (Fe
3
O
4
) and maghemite (
γ
-Fe
2
O
3
) are preferably used since
they are biocompatible and nontoxic to humans. Although nickel and cobalt are highly magnetic,
they are not suitable for administration to humans due to their toxicity [2,60,61]. Magnetic drug
targeting has attracted a great deal of attention. Generally, iron oxide cores are coated with silica,
