Plastic Antibodies - Designing Receptors for the Next Generation of Biosensors - page 109

3 Applications of MIP Nanoparticles

3.1 Drug Delivery

The cross-linked nature and affinity properties of MIPs make them suitable
reservoirs for controlled drug release. This is particularly useful for drugs with a
low therapeutic index (e.g., theophylline), which might cause adverse effects if
their concentration is not kept below a certain threshold value. Chemically or
physically triggered release also can be achieved using MIPs, e.g., when the
polymer interacts with the specific imprinted target moiety, such as a cell surface
receptor overexpressed in a tumor [ 45 ]. Due to their dimensions and high-surface
area, MIP nanoparticles could represent a very interesting solution for these
applications. In a pioneering work by Ciardelli and coauthors, MIP nanoparticles
were used as a drug delivery system for the controlled release of theophylline
(THO) [ 42 ]. Particles of 200 nm diameter were synthesized using a modification of
the precipitation polymerization approach of Ye and coauthors [ 65 ]. However drug
release properties of MIP NPs were not so easy to predict and understand. The
release pattern depended on the fine balance of the strength of monomers-template
interaction, concentration of monomers and polarity of the particles. Jantarat and
coauthors fabricated composite cellulose membranes embedded with MIP
nanoparticles for the transdermal enantioselective release of racemic propranolol
[ 66 ]. The S -enantiomer of this

-blocker is 100-130 times more potent than its
R -isomer, and it would make sense to develop delivery system that would allow
specific delivery of enantiomerically pure compounds [ 67 ]. The authors applied
suspension polymerization in liquid perfluorocarbons to obtain MIP NPs with
diameters in the range 300-500 nm, directly attached to the surface of 3-10

b

m
diameter microspheres [ 68 ]. The release of the S -enantiomer from the composite
membrane was 1.7 times more rapid than the R -enantiomer which proves the
principal feasibility of this approach. However more optimization is required for
this approach to be used as a practical method for clinical applications. The same
group also prepared MIP NPs for S -omeprazole to be used in the fabrication of an
orally administered drug delivery system [ 69 ]. Authors exploited polymerizable
cinchona alkaloids methacryloyl quinine and methacryloyl quinidine as functional
monomers to provide strong anchoring groups. Composite membranes containing
MIP NPs were additionally covered with polyhydroxyethylmethacrylate and
polycaprolactone triol to provide gastroresistant properties. The corresponding
delivery devices exhibited gastroresistant properties and a selective release of
S -omeprazole with an S / R enantiomeric ratio of 2. MIP hydrogel nanospheres
with diameter 270 nm were prepared and used as drug delivery systems for
5-fluorouracil (5-FU) (Fig. 2 , left) [ 41 ]. The use of this drug is hampered by its
short half-life and relatively high toxicity; hence carefully controlled daily
injections are needed to maintain the therapeutic activity [ 70 ]. MIP nanoparticles

m