Biomedical Engineering Reference
In-Depth Information
3.2
The 2R2S Capability of Nanocarriers
3.2.1
2R: Drug Retention in Circulation versus Intracellular
Release
d
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y
3
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2
3.2.1.1 Approaches to Minimize Premature Release from a Stable
Carrier
Figure 3.3 illustrates two examples, an ideal one for the case when the carrier
retains the drug during transport in the blood compartments and the tumor
tissue, but releases it in the tumor cells, and another for a typical case of
undesirable burst release when the carrier releases its drug cargo prematurely
while still circulating in the blood. Such a burst release is generally observed
for polymer particles
9,10
and liposomes.
11,12
As a result, the drug is dumped in
the blood compartments, which causes not only local or systemic toxicity, but
also lowers the drug availability to the tumor and thereby the therapeutic
efficacy.
Although the exact mechanism of burst release is still not fully understood, it
is likely that drug-diffusion resistance can help explain and control it. A study
on a model zero-order device indicated that the rate and extent of burst release
from an otherwise stable carrier were affected by drug solubility and drug
diffusion in an aqueous medium and by the drug loading content.
13
Such
findings inspired more recent approaches to prevent burst release aimed at
enhancing drug loading, inhibiting drug diffusion from the carrier, or both.
Figure 3.3
Sketch of ideal controlled release vs. premature burst release. Adapted
with permission from ref. 8. Copyright 2012 Elsevier.
