Design and Development of Configurational Biomimesis Molecularly Imprinted Polymer Nanoparticles for clinical Analysis of Chiral Drugs / Sirirat Rakkit

Abstract

In this study, it was to develop molecularly imprinted polymer nanoparticles (MIPS nanoparticles) for selective recognition to (R)-, and (S)-thalidomide for assessment of chiral drugs in blood. The selectivity of these materials that enable them to selectively bind the (R)-thalidomide and (S)-thalidomide was created using either as a core shell and non-core shell polystyrene. Firstly, the MIP microspheres were produced using a mixture of methacrylic acid (MAA) and 1-vinyl-2-pyrolidone as a mixed functional monomer that was then cross-linked using N,N'-(1,2- dihydroxyethylene) bisacrylamide (DHEBA), followed by high pressure homoginization. The amounts of the added monomers required to prepare the resultant MIP nanoparticles were optimized. To ensure that the imprinting affect its suitability for the combination of MIPs and other ingredients into a nanosized scale was examined. The performances of the thalidomide imprinted nanoparticles were characterized using Fourier Transform Infrared Spectroscopy (FT-IR), scanning electron microscope (SEM) and a zeta nanosizer. In addition the atomic force microscopy images of the molecularly imprinted nanoparticles were obtained to examine the surface behaviors and force curve analysis. They were mixed with the resin to study the recognition ability by the different MIPs solid-phase extraction for enrichment the two enantiomers and racemic compounds followed by their detection by HPLC. It was shown that each of the enantiomers was recognized by the appropriate MIP and enriched it in the presence of the other biomolecules into the blood. These molecularly imprinted nanoparticles were then attached to a glass substrate and used to form an interdigitated capacitive electrode to develop a highly sensitive and specific sensor to detect each of the enantiomeric drugs. In the preparation processes the monomer ratios were optimized to favor complexation with the crosslinking monomer during the polymerization process. The imprinted thin- films supported on the interdigitated capacitance electrode (IDC) allowed for a rapid binding the individual thalidomide enantiomer after sensing and reaction on the surface. Upon sensor measurement, the resistance signals were gradually increased when increase the concentration of thalidomide, but at a low concentration the resistance signal reached plateau or even reduced which depended on the MIP formulation, because of the release of the thalidomide from the MIPS. They provided the resistance signal with linearity (R2) > 0.990 in the range of 0.025 to 100 μg mL1. The MIP-based IDC showed high sensitivity and selectivity at low concentration detection for thalidomide down to 6.4 ng mL in the presence of biological matrix. This led to interactions between the imprinted nanoparticles and the enantiomers from bovine serum albumin, associated with cholesterol and ceramide that were the interfacial regions on the films. Atomic force microscopy (AFM) and surface enhanced Raman spectroscopy (SERS) were used to examine the nanometered topographical surface onto the surface of the electrode after exposure to the matrix. The results revealed that, the interaction forces on the surface of 100 nN for (R)- thalidomide, but a very low surface force (0.1 nN) for (S)-thalidomide with a high hysteresis and confirmed the interaction of the localized thalidomide enantiomers into the blood component enabled of distinguishing different local regions, better special resolution in the depth detection of 1 Å with the SERS spectra. Thus, the developed MIP nanoparticles with various chemical functional precursors on the films of polymer yielded adjusting in low detection limit of the analyte in blood sample. Taking sensor together with the detection of significant force of enantiomers and SERS images, we can measured the amount of thalidomide relevant within particular biological component exposed to whole blood, that can manipulate the mechanism of molecule interaction of both enantiomers. The MIPs for recognition of (R)- and (S)-thalidomide can be used for enantiomer separation and they have highly potential for the evaluation of efficient drug delivery and the approach to design the assessment for clinical effect.