Biomedical Engineering Reference
In-Depth Information
technologies such as nanotechnology-based imaging (for earlier and better detec-
tion), and targeted nanoparticulate drug and gene delivery systems for improved
treatment alternatives without the systemic side effects. Moreover, nanoparticle
delivery systems can deliver higher dosages of the chemotherapeutic to the tar-
geted tissue while avoiding systemic side effects (Adair
2010
).
In conventional therapy and imaging, drugs do not generally possess tunable
properties that enable enhanced imaging and therapeutic effects. Nanoparticulate
delivery systems, such as calcium phosphate based systems, can overcome the bar-
riers associated with conventional treatments, yielding an improved avenue for
treatment. The potential advantages of nanoparticulate systems over conventional
therapies include the capability to minimize drug degradation during
in vivo
trans-
port (by affording the drug protection from the environment), minimize side effects
(by improved biocompatibility and biodegradability and better targeted delivery)
and increase drug bioavailability and amount of drug delivered to the tissue(s) of
interest (due to high drug loading potential and targetability of nanoparticles)
(Torchilin
2006
; Adair
2010
).
The functionalities of nanoparticulate delivery systems provide the opportunity
(1) for prolonged circulation in the bloodstream, and hence increased likelihood of
accumulation at tumor sites via the enhanced permeation and retention (EPR) effect
or, (2) to specifically bind to cells or tissue of interest via targets for cell surface
receptors, (3) to respond to local stimuli
in vivo
(such as responses to changes in
temperature and pH) and (4) to overcome the cell membrane barrier and avoid the
enzyme filled lysosome where degradation occurs (Torchilin
2006
). Consequently,
desired characteristics of the ideal delivery system include: (1) non-toxic starting
materials and degradation products, (2) small size (in the range of 10-200 nm) for
improved uptake, (3) encapsulation of the active agent within the delivery system (as
opposed to surface decoration or adsorption where the active agent is not protected
from the environment), (4) colloidal stability of the delivery system (to prevent
agglomeration
in vivo
during transport), (5) suitable clearance mechanism (to avoid
side effects due to drug laden particles), (6) long clearance times (to allow adequate
time for the delivery system to reach target cells and undergo endocytosis), (7) con-
trolled release of active agent (such as a pH trigger) and (8) targetability of the
delivery system (to enable delivery of particles to cells of choice) (Adair
2010
).
The innate properties of calcium phosphates (such as biocompatibility and pH
dependent solubility) combined with the ability to carefully engineer specific char-
acteristics (size, surface functionalization, etc.) into the delivery system to suit a
specific need or carry out a certain function make calcium phosphate based delivery
systems especially useful in delivery based applications.
This chapter focuses on the potential use and efficacy of calcium phosphate
based nanoparticles in biomedical applications involving imaging and therapy. An
overview is presented of the inherent properties of the calcium phosphate system
and practical aspects of calcium phosphate based systems that satisfy the criteria
outlined earlier for an ideal delivery system. It is demonstrated that the inherent
properties of calcium phosphate based systems provide advantages in the delivery
and release of bio-agents (such as drugs, nucleic acids or fluorescent molecules
for imaging).
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