Biomedical Engineering Reference
In-Depth Information
anisamide-LCP particles. The results indicate improvement in gene silencing for
targeted particles in both
in vitro
and an
in vivo
animal model. Barth
et al
. target
CPSNPs with avidin-human holotransferrin and avidin-anti-CD71 antibody for
breast cancer and with a ten amino acid gastrin (gastrin-10) polypeptide for pancre-
atic cancer via avidin-biotin and PEG-maleimide coupling, respectively. The
enhanced delivery of gastrin-10 targeted CPSNPs to pancreatic cancer cells as
compared to PEGylated CPSNPs and biotinylated avidin-pentagastrin CPSNPs is a
promising result of the study (Barth
2010
). While the methoxy-terminated PEG
(passively targeted) CPSNPs display effective targeting, the anti-CD71-avidin tar-
geted CPSNPs are the most effective for delivery to breast cancer cells (Barth
2010
). However, the anti-CD71-avidin CPSNPs have non-specific binding in the
stomach (Barth
2010
). The off-target accumulation of the CPSNPs in the stomach
is attributed to the diets of the mice which are high in biotin (which likely interacts
with the avidin on the surface of the particles) and underscores an inherent limita-
tion of the avidin-biotinylated bio-conjugation scheme for
in vivo
models (Barth
2010
). The results of this study exemplify the importance of identifying appropriate
target molecules and conducting both
in vitro
and
in vivo
studies to fully evaluate
efficacy of the drug delivery or bioimaging nanoparticle system (Barth
2010
).
3
Overview of Calcium Phosphate Systems - Synthesis
and Architectures
There are various approaches in the encapsulation of therapeutic agents using cal-
cium phosphate. Aside from the pure calcium phosphate system, the incorporation
of polymers, liposomes and other organic and inorganic materials as well as various
architectures to improve ease of encapsulation have been developed. The basic
properties of some of these systems are addressed in this section but with new ideas
and systems constantly being developed, this segment serves more as an introduc-
tion to the area rather than a detailed account.
Of great importance is to distinguish between encapsulation and surface decora-
tion (adsorption). Table
1
summarizes a few of the calcium phosphate based deliv-
ery systems classified based on their architecture - encapsulation, surface
decoration or a combination of the two architectures. As discussed earlier, the
encapsulation of the active agent is a better alternative to the traditional use of
calcium phosphate using surface decoration. In an encapsulation model, the active
agent is protected within the delivery vehicle. Therefore, the active agent does not
degrade due to interactions with other molecules in the blood stream
en route
to
the cells of interest. In the surface decoration model, which has been practiced
since 1973 (Graham
1973
), the active agent is on the outer surface of the delivery
vehicle and is susceptible to degradation while in the bloodstream. The ability to
control dispersion, the EPR effect, and targeting are all compromised by the sur-
face decoration approach for calcium phosphates. Thus, surface decoration does
not readily permit
in vivo
studies, although
in vitro
evaluations may indicate
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