We have developed a reversible, biocompatible, “self-programmed”
PLGA [poly(lactic-co-glycolic acid)] nanoparticle-based
optical biosensor capable of sensing and continuous monitoring of
glucose above the physiologically relevant threshold value (100–125
mg/dL) as well as “on-demand” insulin delivery via an
“On–Off” technique. We have carefully surface
engineered the PLGA nanoparticle using amino dextran-fluorescein (A-DexFl)
and amino-phenyl boronic acid (A-PBA) to exploit the binding affinity
of boronic acids with that of cis-1,2 diols of dextran/glucose.
Initially, the dextran chains wrap the nanoparticle surface due to
its high affinity toward A-PBA (K
b = 6.1
× 106 M–1). The close proximity
of the fluorophores with that of A-PBA quenches the fluorescence,
resulting in an “Off” state. On the addition of glucose,
it competes with A-DexFl to bind with A-PBA. Above a certain threshold
concentration of glucose, the binding affinity overcomes (K
b = 6.3 × 107 M–1) the dextran-A-PBA binding. This opens-up the wrapped A-DexFl chains
from the nanoparticle surface and results in an increased distance
between the fluorophore and A-PBA, triggering the “On”
state. The activation of the On–Off state can be finely tuned
in the desired range of physiologically relevant glucose concentrations
by varying the ligand ratios on the PLGA surface. The nanoparticle
core has also been used as an insulin reservoir to trigger the drug
release in the “On” state. We have obtained ∼53%
encapsulation efficiency and ∼20% loading efficiency for insulin
loading. Once the glucose concentration falls beyond the detection
range, the dextran chains collapse on the nanoparticle surface with
a suspension in drug release. The process is solely controlled by
the competition and multivalent binding affinity between glucose,
A-DexFl, and A-PBA, which allows it to be “self-programmed”
and “self-regulated” with continuous monitoring up to
8–10 cycles over a 72 h time period. A sustained drug release
has been found with ∼70% of released drug over a period of
72 h, although this release is insignificant in the absence of glucose.
Several control experiments have been performed to optimize the sensor
design.
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