Poly (methacrylic acid)‐based molecularly imprinted polymer nanoparticles containing 5‐fluourouracil used in colon cancer therapy potentially

The objective of this work was to synthesize molecularly imprinted polymer (MIP) nanoparticles based on methacrylic acid (MAA) monomer with a high selectivity against an anti‐cancer drug, 5‐fluorouracil (5‐FU), as a template. In this case, the nanoparticles were prepared via precipitation polymerization in the presence of ethylene glycol dimethacrylate as cross‐linker and azobisisobutyronitrile as initiator. Besides, 3 independent variables including MAA: 5‐FU molar ratio (X₁), temperature (X₂), and time (X₃) were investigated utilizing response surface methodology. The scanning electron microscopy and dynamic light scattering resulted the average diameter of approximately 65 nm, and the MIP nanoparticle sample with the imprinting factor of 1.57 was polymerized in optimized conditions as follows: X₁ = 6: 1, X₂ = 60°C, and X₃ = 3 days in acetonitrile as porogenic solvent. Also, Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis confirmed the formation of MAA/5‐FU complex and lower thermal stability of the washed MIP sample than the unwashed MIP and non‐imprinted polymer (NIP) samples, respectively. Moreover, the optimized MIP nanoparticles have more controlled release of 5‐FU rather than the NIP sample. Finally, the flow cytometry showed that 5‐FU‐loaded MIP sample has the highest apoptosis of human colon cancer cell line, HCT‐116, after 3 days compared with NIP sample and also the exclusive use of drug.     

Molecularly imprinted beads with double thermosensitive gates for selective recognition of proteins

A new approach is reported on the use of poly(N-isopropylacrylamide) (PNIPAM)-coated molecularly imprinted beads (coated MIP beads) for controlling the release of protein. The coated MIP beads were composed of double layers, an internal thermosensitive lysozyme-imprinted layer, and an external PNIPAM layer. The coated MIP beads were prepared by two-step surface-initiated living-radical polymerization (SIP). In this systemic study, the coated MIP beads had good selectivity to the template protein (lysozyme) and temperature stimulus-responsive behavior, both of which were superior to those of MIP beads having a layer of thermosensitive lysozyme-imprinted polymer only. Using the coated MIP beads, reference proteins and the template lysozyme could be released separately at 38 °C and at 23 °C. The corresponding coated non-imprinted beads (coated NIP beads) did not have such double thermosensitive “gates” with specific selectivity for a particular protein. The proposed smart controlled imprinted system for protein is attractive for chemical carriers, drug-delivery system, and sensors.     

Probing cavity versus surface preference of fluorescent template molecules in molecularly imprinted polystyrene microspheres

Functional polystyrene (PS) crosslinked microbeads were developed by dispersion polymerization as fluorescent molecularly imprinted polymers (MIPs) having cavities with specific recognition sites. The functional azobenzene molecule modified with pyridine was self‐assembled with Pyrenebutyric acid (template molecules), and introduced during the second stage of dispersion polymerization of polystyrene. The template molecule was removed from MIP by Soxhlet using acetonitrile as solvent. Non imprinted polymer (NIP) having no template was also synthesized for comparative study. Fluorescence spectroscopy could be used as a tool to derive insight into the location of the template molecules on the MIP or NIP. The template molecules were adsorbed on the surface of the NIPs during binding studies, which was evidenced from the pyrene excimeric emission observed at 440 nm. The template binding efficiency of the NIPs were much lower compared to MIPs. Pyrene emission from MIP upon rebinding showed typical monomeric emission in the 375–395 nm range, confirming its location in isolated cavities. In rebinding studies of the template molecules, the MIPs selectively took up the template for which the cavity was designed, which demonstrated their selectivity towards template molecules. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 1558–1565     

Photoregulated uptake and release of drug by an organic–inorganic hybrid sol–gel material

A photo-responsive molecularly imprinted sol–gel organic-inorganic hybrid material prepared by covalent imprinting of the template-functional monomer complex formed between 4,4′-dihydroxylazobenzene and ibuprofen was developed to explore the photo-regulated uptake and release of drug by a silicate-based smart molecularly imprinted materials. After imprinting, the template molecules (ibuprofen) were removed via hydrolysis in acid, and accurate cavities were left, which could be used as the receptor recognition sites for ibuprofen. The new organic–inorganic hybrid material shows specific affinity to ibuprofen and reversible uptake and release of ibuprofen upon alternate irradiation at 365 and 440 nm, respectively. The favorable binding strength of the imprinted receptor sites in the molecularly imprinted polymer (MIP) for ibuprofen is found to be 2.28 × 10³ M⁻¹. Density of receptor sites in the MIP material was 4.0 μmol/g—MIP.     

A selective molecularly imprinted polymer-solid phase extraction for the determination of fenitrothion in tomatoes

A new and selective sorbent for molecularly imprinted solid-phase extraction (MISPE) was developed and applied for the determination of residues of fenitrothion (FNT) in tomatoes, using HPLC coupled to photodiode array detection (HPLC-DAD). Using FNT as the template molecule, methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as the cross-linker, toluene as the porogenic solvent, and bulk polymerization as the synthetic method, a molecularly imprinted polymer (MIP) was synthesized. In order to choose the medium which promotes the best molecular recognition of FNT by the MIP, the adsorption of FNT by the MIP was studied in different media containing acetonitrile and toluene. Besides FNT, three structurally related compounds were used to evaluate the selectivity of the FNT-molecularly imprinted polymer. The MIP exhibited the highest selective rebinding to FNT. The method developed was validated, using fortified blank tomato samples. The extraction efficiency was 96%. The limits of detection and quantitation were 0.050 and 0.130 μg g⁻¹, respectively. The intra-day precision was 5.9% and the inter-day precision 8.1%. The accuracy was higher than 89% for a concentration level around the maximum residue limit of 0.5 μg g⁻¹.     

Synthesis of poly(2‐hydroxyethyl methacrylate)‐based molecularly imprinted polymer nanoparticles containing timolol maleate: morphological,thermal, and drug release along with cell biocompatibility studies

This work was aimed to synthesize and characterize poly(2‐hydroxyethyl methacrylate) [poly (HEMA)]‐based molecularly imprinted polymer nanoparticles (MIP NPs) containing timolol maleate (TM) via precipitation polymerization. The molecular structures of the MIP and non‐imprinted polymer (NIP) NPs were compared by means of Fourier transform infrared spectroscopy. The morphological observations by using scanning electron microscopy and transmission electron microscopy confirmed the formation of MIP NPs as small as 128 nm in average diameter with appropriate synthesis conditions. Thermal behaviors of the samples were also studied by the use of thermogravimetric analysis and differential scanning calorimetry. By considering a series of key factors such as monomer : template ratio, cross‐linker type, pH, and temperature, the sample with promising characteristics was found to be that of HEMA : TM ratio of 10:1, 40 mmol of ethylene glycol dimethacrylate as cross‐linker, and polymerization temperature of 60°C in acetonitrile as porogenic solvent. Furthermore, the ultraviolet‐visible (UV‐vis) spectrophotometry results proved a controlled release of TM from the MIP NP samples compared with NIP ones at extended periods. Moreover, the cytotoxicity of the MIP and NIP NPs samples was evaluated on mesenchymal stem cells, and the obtained observations showed that they had no adverse side effect on the living cells; especially the surface of the MIP NPs sample depicted highly cell's biocompatibility. Finally, the outcomes from designed different experiments conducted us that the HEMA‐based MIP NPs have great potential as an ocular nanocarrier for TM delivery. Copyright © 2016 John Wiley & Sons, Ltd.     

硅胶表面扑灭津分子印迹材料的制备及性能表征

以扑灭津为模板分子,在甲苯溶液中经三步反应合成了基于硅胶表面修饰的分子印迹聚合物,并探讨了聚合物制备工艺,验证了聚合物的结构。红外1726cm-1指认印迹膜中的羰基特征峰,元素分析表明印迹材料含碳量18%,N2吸附实验表征印迹膜厚度为0.3nm。应用高效液相色谱-质谱考察了扑灭津和其它3种三嗪农药水溶液中的竞争吸附特性。研究表明:本法制备的表面印迹材料对4种三嗪类农药的吸附均优于参比材料。     

Developing imprinted polymer nanoparticles for the selective separation of antidiabetic drugs

In this study, new molecularly imprinted polymer (MIP) nanoparticles are designed for selective recognition of different drugs used for the treatment of type 2 diabetes mellitus, i.e. sitagliptin (SG) and metformin (MF). The SG‐ and MF‐imprinted polymer nanoparticles are synthesized by free‐radical initiated polymerization of the functional monomers: methacrylic acid and methyl methacrylate; and the crosslinker: ethylene glycol dimethacrylate. The surface morphology of resultant MIP nanoparticles is studied by atomic force microscopy. Fourier transform infrared spectra of MIP nanoparticles suggest the presence of reversible, non‐covalent interactions between the template and the polymer. The effect of pH on the rebinding of antidiabetic drugs with SG‐ and MF‐imprinted polymers is investigated to determine the optimal experimental conditions. The molecular recognition characteristics of SG‐ and MF‐imprinted polymers for the respective drug targets are determined at low concentrations of SG (50–150 ppm) and MF (5–100 ppm). In both cases, the MIP nanoparticles exhibit higher binding response compared to non‐imprinted polymers. Furthermore, the MIPs demonstrate high selectivity with four fold higher responses toward imprinted drugs targets, respectively. Recycled MIP nanoparticles retain 90% of their drug‐binding efficiency, which makes them suitable for successive analyses with significantly preserved recognition features.     

Removal of endocrine‐disrupting compounds from water using macroporous molecularly imprinted cryogels in a moving‐bed reactor

Highly efficient removal of endocrine‐disrupting compounds (EDCs) such as 17β‐estradiol (E2), 4‐nonylphenol (NP) and atrazine from water was achieved using a novel macroporous adsorption medium. The medium consisted of a macroporous poly(vinyl alcohol) (PVA) cryogel with molecularly imprinted polymer (MIP) particles embedded in it. The MIP was prepared using E2, NP and atrazine as templates. The macroporous composite molecularly imprinted cryogels were formed inside the open‐ended protective shells, known as Kaldnes carriers. These adsorbents (defined as Macroporous Gel Particles, MGPs) were evaluated on the removal of E2, NP and atrazine from water using different column configurations, namely column filled with the MGPs (packed‐bed column) and in moving‐bed reactors (defined here as moving‐bed MGPs reactor). Complete binding (> 99%) of E2 from a spiked aqueous solution (1 mg/L) was achieved using E2‐MIP/MGPs in a moving‐bed MGPs reactor at the retention time in the reactor of 4 min, while only 77% was bound to the nonimprinted medium (NIP/MGPs). Similar results were also obtained for the adsorption medium imprinted with atrazine. All contaminants studied (E2, atrazine and NP) were effectively removed from water at low (environmentally relevant) concentrations by the respective adsorption medium.     

Preparation of a pH-sensitive pantoprazole-imprinted polymer and evaluation of its drug-binding and -releasing properties

The aim of this work was to synthesize a pantoprazole-imprinted polymer(MIPs)and study its binding and release properties in an aqueous media.Methacrylic acid(MAA),methacrylamide(MAAM),hydroxyethyl methacrylate(HEMA),and 4-vinyl pyridine(4VP)were tested as functional monomers.Different solvents were also applied as polymerization media under heat or UV radiation.The optimized MIP was prepared in chloroform as a solvent,4-vinyl pyridine as a functional monomer,and ethylene glycole dimethacrylate(EGDMA)as a crosslinker monomer under UV irradiation.Binding and release properties of MIP were studied in comparison with a non-imprinted polymer(NIP)in aqueous media,at different pH values.The protective effect of polymer for drugs against acidic conditions was evaluated at pH 2.Results indicated that the MIP had superior binding properties compared to NIP for pantoprazole.The percentage of drug released from MIP was significantly less than from NIP at all pH values,which was attributed to the presence of imprinted cavities in the MIP matrix.MIP also had a stronger protective effect for pantoprazole in acidic media,in comparison with NIP.     

Preparation and characterization of protein molecularly imprinted polysiloxane using mesoporous calcium silicate as matrix by sol–gel technology

Calcium silicate particles containing mesoporous SiO₂ on the surface (CaSiO₃@SiO₂) were prepared by acid modification of calcium silicate with diluted hydrochloric acid. Bovine serum albumin (BSA) molecularly imprinted polysiloxane (MIP) was synthesized using silane as the functional monomer, BSA as the template and CaSiO₃@SiO₂ particles as the matrix in an aqueous phase. SEM, granulometry, FT-IR and BET analysis were used to characterize the protein MIP. Influence factors on the rebinding capacity of the MIP were investigated, such as the pH in treating CaSiO₃, eluent type and silane proportion. The mass of BSA loading and rebinding on CaSiO₃@SiO₂ and MIP was investigated. The adsorption and recognition properties of the MIP were evaluated and the results showed that the MIP exhibited an obvious improvement in terms of rebinding capacity for BSA as compared with non-imprinted polysiloxane (NIP). BSA imprinted polysiloxane could recognize the template protein by using Lys, Ova, Hb, and Glo as control proteins, and the selectivity factor (β) was above 2.3. The rebinding capacity of BSA imprinted polysiloxane for BSA reached 81.31 mg/g, which was 2.25 times of NIP.     

Selective Solid‐phase Extraction of Bisphenol A Using a Novel Stir Bar Based on Molecularly Imprinted Monolithic Material

In this paper, a novel monolithic stir bar based on molecularly imprinted polymer (MIP) was firstly developed by filling modified neodymium magnet (Nd₂Fe₁₄B) powders into a glass tube (60 × 4 mm), followed by the imprinted grafting with bisphenol A (BPA) as the template molecule by thermal polymerization. It has been successfully used for the stir bar sorptive extraction (SBSE) and its extraction performance illustrated that the MIP‐encapsulated stir bar had stronger affinity to the template molecule, compared with the stir bar based on the non‐imprinted molecularly polymer (NIP). Under the optimal extraction conditions, a simple method based on the coupling of MIP‐SBSE with high performance liquid chromatography (HPLC) was used for the selective determination of the model mixtures of BPA, 4‐phenylphenol (PP) and phenol (P) in bottled water. The recoveries of BPA, PP and P were in the range of 88.5‐96.1%, 78.2‐89.7%, 81.3‐89.5% at three spiked levels, respectively, demonstrating that higher extraction and the specific absorption occurred between the template molecule and the prepared MIP stir bar.     

Development of solid‐phase microextraction coupled with liquid chromatography for analysis of tramadol in brain tissue using its molecularly imprinted polymer

In this work, performance of a molecularly imprinted polymer (MIP) as a selective solid‐phase microextraction sorbent for the extraction and enrichment of tramadol in aqueous solution and rabbit brain tissue, is described. Binding properties of MIPs were studied in comparison with their nonimprinted polymer (NIP). Ten milligrams of the optimized MIP was then evaluated as a sorbent, for preconcentration, in molecularly imprinted solid‐phase microextraction (MISPME) of tramadol from aqueous solution and rabbit brain tissue. The analytical method was calibrated in the range of 0.004 ppm (4 ng mL⁻¹) and 10 ppm (10 μg mL⁻¹) in aqueous media and in the ranges of 0.01 and 10 ppm in rabbit brain tissue, respectively. The results indicated significantly higher binding affinity of MIPs to tramadol, in comparison with NIP. The MISPME procedure was developed and optimized with a recovery of 81.12–107.54% in aqueous solution and 76.16–91.20% in rabbit brain tissue. The inter‐ and intra‐day variation values were <8.24 and 5.06%, respectively. Finally the calibrated method was applied for determination of tramadol in real rabbit brain tissue samples after administration of a lethal dose. Our data demonstrated the potential of MISPME for rapid, sensitive and cost‐effective sample analysis.     

Synthesis of monodispersed molecularly imprinted polymer particles for high-performance liquid chromatographic separation of cholesterol using templating polymerization in porous silica gel bound with cholesterol molecules on its surface

Monodispersed molecularly imprinted polymer particles selective for cholesterol were prepared by the copolymerization of styrene and divinylbenzene in the presence of template silica gel particles (particle size: 5 μm; pore size: 10 nm) functionalized with cholesterol on the surface, followed by dissolution of the cholesterol-bonded silica gel with a NaOH aqueous solution. Transmission and scanning electron micrographs of the molecularly imprinted polymer (MIP) particles revealed good monodispersity and porous structure. The MIP particles were packed into a high performance liquid chromatographic column, and its recognition ability of cholesterol was evaluated using cholesterol, cholesterol esters and fatty acid methyl esters by comparison with the non-imprinted polymer (NIP) particles prepared from styrene and divinylbenzene without cholesterol. The MIP particles showed a high affinity for cholesterol and cholesterol esters (K(MIP)'/K(NIP)' > 5.7).     

Synthesis and characterization of molecularly imprinted polymers for selective solid-phase extraction of pseudoephedrine

Molecular imprinted solid-phase extraction (MISPE) is a well known technique for the selective extraction and pre-concentration of analytes, are present at low levels in chemically complex materials. Herein, water-soluble, molecularly imprinted polymers (MIP) were prepared for solid-phase extraction of pseudoephedrine hydrochloride (PSE), which was monitored at 256 nm by the UV spectroscopy. MISPE conditions were optimized to allow the selective and determination of PSE in aqueous samples and composite materials, such as biological fluids and human urine. MIP was prepared by precipitation polymerization method, using methacrylic acid as a functional monomer and ethylene glycol dimethacrylate as a cross-linking agent in either acetonitrile or chloroform. The results suggest that the obtained MISPE exhibits high affinity for PSE, and the imprinted polymer demonstrates much higher efficiency than a non-imprinted polymer (NIP). The imprinting-induced extraction was confirmed by the determination of recovery values for NIP (4%) and MIP (80%) polymers, respectively. The binding capacity of the MIP for PSE was found of 47.6 mg g⁻¹.     

Surface plasmon resonance sensor chips for the recognition of bovine serum albumin via electropolymerized molecularly imprinted polymers

In this paper,a surface plasmon resonance(SPR)sensor chip for detection of bovine serum album(BSA)was prepared by electropolymerization of 3-aminophenylboronic acid(3-APBA)based on molecularly imprinted polymer(MIP)technique.The surface morphology of MIP and non-imprinted(NIP)flms were characterized by scanning electroscopy(SEM).SEM images exhibited nanoscale cavities formed on the MIP films surface homogeneously due to the removal of BSA templates.The effects of pH,ion strength of rebinding BSA,the specific binding and selective recognition were studied for MIP films.Results indicated that the BSA-imprinted films exhibited a good adsorption of template protein(0.02–0.8 mg/mL)in0.05 mol/L sodium phosphate buffer at pH 5.0 with the limit of detection(LOD)of 0.02 mg/mL.     

Via protoporphyrin to the synthesis of levofloxacin‐imprinted polymer

A new molecularly imprinted polymer (MIP) for levofloxacin was prepared by the combined use of methacrylic acid and protoporphyrin as functional monomers. The adsorption properties of resultant imprinted polymers were evaluated by equilibrium rebinding experiments. The highest binding capacity of levofloxacin achieved from the optimized imprinted polymer in acetonitrile was 246.26 µmol/g with an imprinting factor of 2.05. A ?uorescence quenching effect was observed when a protoporphyrin‐based imprinted polymer was incubated in the solutions of levofloxacin. The results indicated that the protoporphyrin‐based MIPs were able to create higher binding cavities for template compared with MIPs using only methacrylic acid as a functional monomer. It should be expected that the cooperative use of the protoporphyrin with supplemental different functional monomers may be an alternative to obtain MIP with the improvement of the selectivity. Copyright © 2010 John Wiley & Sons, Ltd.     

Molecularly imprinted polymer for solid‐phase extraction of ephedrine and analogs from human plasma

A molecularly imprinted polymer (MIP) was synthesized and evaluated to selectively extract ephedrine from human plasma. The MIP synthesis was performed in chloroform with methacrylic acid as a functional monomer and the target alkaloid as a template molecule. The resulting MIP was applied to the selective extraction of ephedrine from a pure aqueous medium. A recovery about 74% was obtained using the MIP with only 7% on the nonimprinted polymer (NIP). A very straightforward selective SPE procedure was then successfully applied to the direct extraction of ephedrine from spiked human plasma with a high extraction recovery (68%) on the MIP with no recovery on the NIP. Moreover, the MIP was used for the selective extraction of catecholamine neurotransmitters, i.e. adrenaline and noradrenaline.     

Response surface methodology approach for the preparation of a molecularly imprinted polymer for solid‐phase extraction of fenoxycarb pesticide in mussels

The aim of this work was to develop an efficient method for the selective extraction and analysis of fenoxycarb, a carbamate pesticide, in mussel samples using a molecularly imprinted solid‐phase extraction device. The optimization of molecularly imprinted polymer synthesis was performed using the experimental design under the response surface methodology approach. A fast rebinding study and Freundlich isotherm adsorption were carried out to calculate binding capacity B, site number n, and affinity constant K_f. The optimum molecularly imprinted polymer was successfully used as sorbent of a solid‐phase extraction cartridge for the determination of fenoxycarb in real mussel samples. The range of linearity was 0.3–30 mg/L with a correlation coefficient of 0.991. The limit of detection was 0.247 mg/kg. The recovery of fenoxycarb extracted from mussel samples of Mediterranean sea was 97% (n = 3) with relative standard deviation between 6 and 7% proving the reliability of the developed method.     

High Selective Parathion Voltammetric Sensor Development by Using an Acrylic Based Molecularly Imprinted Polymer‐Carbon Paste Electrode

The design and construction of an extra high selective voltammetric sensor for parathion by using a molecularly imprinted polymer (MIP) as recognition element was introduced. A parathion selective MIP and a nonimprinted polymer (NIP) were synthesized and then incorporated in the carbon paste electrode. The MIP‐CP electrode showed very high recognition ability in comparison to NIP‐CP. It was shown that electrode washing after parathion extraction, led to enhanced selectivity. Some parameters affecting the sensor response were optimized and then the calibration curve was plotted. A dynamic linear range of 1.7–900 nM was obtained. The detection limit of the sensor was calculated as 0.5 nM. This sensor was used successfully for parathion determination in real samples such as ground water and vegetables.