Biomedical Engineering Reference
In-Depth Information
as pH-sensitive molecules [65]. Embedding dye-loaded NCs into a permeable matrix
addresses a long-standing challenge of reconciling fast response of chemosensors
with long-term stable performance of practical optical sensors. This concept can be
expanded into biocompatible and/or biodegradable matrices to create implantable
devices.
Cargo release from capsules can be controlled remotely and on demand by using
an external stimulus. For biomedical applications, one of the extensively used
external release triggers is NIR radiation because this stimulus can be applied in a
focused area that allows localized release from individual capsules (Fig. 4.19). For
therapeutic applications, the release of capsule cargo through an inherent biological
stimulus is of immense interest. Changes in the environmental pH, salinity, and tem-
perature are commonly exploited environmental triggers that have been used to
induce release in polymer carriers. In addition, significant advances were reported in
the field of triggered release using other intrinsic stimuli, including changes in redox
potential (thiol-disulfide exchange), enzymatic degradation, change of solvent com-
position, and degradation in response to the presence of a specific metabolite.
Recently, we created NCs capable of burst release of encapsulated content upon
contact with blood [84]. Rapid release is achieved by the expansion of intrinsic nano-
pores in the NC shell caused by the conformational change due to interactions with
albumin.
In vivo
imaging showed rapid release of the model compound indocyanine
green (ICg), an FDA-approved NIR fluorescent dye (Fig. 4.20).
To treat some forms of cancer and viral infections, a photosensitizer (hypocrellin
B (HB)) was loaded into capsules applying a solvent exchange step, where ethanol
was used as a solvent for HB [85]. upon exposure to light, HB generates singlet
oxygen, which is cytotoxic and induces cell death. However, HB does not display
cytotoxicity in the absence of the light irradiation. upon incubation with the living
cells, the HB-loaded capsules were efficiently internalized and appeared to be non-
cytotoxic. However, upon irradiation with 488 nm light, the cell viability dropped by
70%. In this
in vitro
experiment, the light addressable microcapsules emerge as
promising candidates for the site-specific delivery of drug molecules that need to be
placed into a protective container on the way to the biological target.
Cancer therapy is a rapidly emerging application, due to the ability of polymer-
somes to load both hydrophilic and hydrophobic anticancer drugs within their lumen
and membrane cores, respectively. Both hydrophilic (doxorubicin (DOX)) and
hydrophobic (paclitaxel) anticancer drugs have been loaded simultaneously within
PEO-PLA and PEO-PCL polymersomes (generated by mixing these hydrolytically
degradable block copolymers (1:3 mol/mol) with inert PEO-PBD) by Ahmed,
Discher, and coworkers [86, 87]. These polymersomes were not only able to deliver
these drugs into a human breast tumor implanted into mice; growth retardation and a
reduction of the tumor area were also observed. At a time point of 5 days after IV tail
injection of the polymersomes into the mice, the tumor shrank to less than 50% of its
original size. Due to the biodegradability of the ester blocks comprising these poly-
mersomes and the blending of a degradable block copolymer with a chemically inac-
tive block copolymer, the drug release rate could be controlled, with the mildly
acidic environment within cellular endosomes triggering faster ester hydrolysis and
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