Dey, Gaurav Ranjan and Saha, Arindam (2021) Surface Engineered PLGA Nanoparticle for Threshold Responsive Glucose Monitoring and “Self-Programmed” Insulin Delivery. ACS Biomaterials Science & Engineering. ISSN 2373-9878 (Submitted)

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Abstract

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 (Kb = 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 (Kb = 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−Offstate 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.

Item Type:	Article
Subjects:	Engineering Materials
Divisions:	UNSPECIFIED
Depositing User:	Bidhan Chaudhuri
Date Deposited:	03 Sep 2021 07:03
Last Modified:	03 Sep 2021 07:03
URI:	http://cgcri.csircentral.net/id/eprint/5165

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