Reduction-responsive molecularly imprinted nanogels for drug delivery applications

Degradable molecularly imprinted polymers (MIPs) with affinity for S-propranolol were prepared by the copolymerization of methacrylic acid as functional monomer and a disulfide-containing cross-linker, bis(2-methacryloyloxyethyl)disulfide (DSDMA), using bulk polymerization or high dilution polymerization for nanogels synthesis. The specificity and the selectivity of DSDMA-based molecularly imprinted polymers toward S-propranolol were studied in batch binding experiments, and their binding properties were compared to a traditional ethylene glycol dimethacrylate (EDMA)-based MIP. Nanosized MIPs prepared with DSDMA as crosslinker could be degraded into lower molecular weight linear polymers by cleaving the disulfide bonds and thus reversing cross-linking using different reducing agents (NaBH₄, DTT, GSH). Turbidity, viscosity, polymer size and IR-spectra were measured to study the polymer degradation. The loss of specific recognition and binding capacity of S-propranolol was also observed after MIP degradation. This phenomenon was applied to modulate the release properties of the MIP. In presence of GSH at its intracellular concentration, the S-propranolol release was higher, showing that these materials could potentially be applied as intracellular controlled drug delivery system.

Degradable molecularly imprinted polymers were prepared using redox sensitive cross-linkers and applied as intracellular drug delivery system to address the biocompatibility and cytotoxicity issues encountered with these synthetic polymers.     

Novel fluorescence sensor for the selective recognition of tetracycline based on molecularly imprinted polymer-capped N-doped carbon dots

A novel fluorescent probe based on molecularly imprinted polymers (MIPs) coupled with N-doped carbon dots (CDs) was prepared and used for specific recognition and sensitive determination of tetracycline (TC). N-doped CDs were synthesized using citric acid as a carbon source and ethylenediamine as a nitrogen source by a microwave assisted pyrolysis method. The determination conditions such as the solvents, material amount, pH value, and temperature were optimized. The CDs-MIPs have the best quenching on TC in water. The proposed method used for TC determination in milk powder samples had a detection limit of 0.054 μg mL⁻¹ and a wide range of 0.5–30 μg mL⁻¹. Meanwhile, satisfactory recoveries were obtained ranging from 95 to 108%. Oxytetracycline, chlorotetracycline and most of the coexisting substances showed no obvious interference indicating that the CDs-MIP probe exhibited high selectivity due to the presence of imprinted sites. Charge transfer from CDs-MIPs to TC may be through the mechanism of fluorescence quenching. This work gives a feasible strategy for the synthesis of N-doped carbon dot based molecularly imprinted polymers used as a fluorescent sensor in the food analysis field.

A novel fluorescent probe based on MIP coupled with N-doped CDs was prepared and used for sensitive recognition of tetracycline.     

Nano-molecularly imprinted polymers (nanoMIPs) as a novel approach to targeted drug delivery in nanomedicine

Molecularly imprinted polymers – MIPs – denote synthetic polymeric structures that selectively recognize the molecule of interest against which MIPs are templated. A number of works have demonstrated that MIPs can exceed the affinity and selectivity of natural antibodies, yet operating by the same principle of “lock and key”. In contrast to antibodies, which have certain limitations related to the minimal size of the antigen, nanoMIPs can be fabricated against almost any target molecule irrespective of its size and low immunogenicity. Furthermore, the cost of MIP production is much lower compared to the cost of antibody production. Excitingly, MIPs can be used as nanocontainers for specific delivery of therapeutics both in vitro and in vivo. The adoption of the solid phase synthesis rendered MIPs precise reproducible characteristics and, as a consequence, improved the controlled release of therapeutic payloads. These major breakthroughs paved the way for applicability of MIPs in medicine as a novel class of therapeutics. In this review, we highlight recent advances in the fabrication of MIPs, mechanisms of controlled release from the MIPs, and their applicability in biomedical research.

The review highlights the recent advances in fabrication of molecularly imprinted polymers and their applicability for drug delivery.     

Biomimetic enzyme-linked immunoassay based on a molecularly imprinted 96-well plate for the determination of triazophos residues in real samples

In this study, a direct competitive biomimetic enzyme-linked immune-sorbent assay (BELISA) based on a molecularly imprinted nanomembrane as an artificial antibody was developed for the determination of triazophos in real samples. The imprinted film was directly synthesized on the well surface of a 96-well plate using a dummy molecular template under the conditions of thermal polymerization. The developed BELISA using a hapten of triazophos as an enzyme-labeled probe is much more sensitive, simple, quick, steady and inexpensive than the other instrumental and immuno assay methods. Under optimal conditions, the linear range of the method was 0.001–10 000 μg L⁻¹ with a good regression coefficient of 0.977. The sensitivity (IC₅₀) and the limit of detection (LOD) of BELISA were 428 μg L⁻¹ and 0.001 μg L⁻¹, respectively. This method was performed to detect triazophos in cabbage and apple samples, and showed excellent recovery and relative standard deviations (RSDs) ranging from 70.5 to 119.8% and from 5.2 to 19.7%, respectively. The results correlated well with those obtained using high performance liquid chromatography-tandem mass spectrometry.

In this study, a direct competitive biomimetic enzyme-linked immune-sorbent assay (BELISA) based on a molecularly imprinted nanomembrane as an artificial antibody was developed for the determination of triazophos in real samples.     

Dual roles of 3-aminopropyltriethoxysilane in preparing molecularly imprinted silica particles for specific recognition of target molecules

3-Aminopropyltriethoxysilane (APTES) is a silane widely used to supply amino groups for further modifications on various materials, but it is less studied as a catalyst to catalyze sol–gel silica polymerization. Here, by using APTES as the catalyst instead of the conventional basic catalysts, a novel strategy was developed to prepare silica-based molecularly imprinted polymers (MIPs). Meanwhile, APTES was employed as the functional monomer to create imprinted nanocavities for specific recognition of target molecules. The as-synthesized MIP exhibited ultra-high recognition capability due to the elimination of the detrimental effect on the imprinting performance caused by the additional catalysts. The preparation process, specificity, pH effect, binding capacity and affinity of the MIP were studied in detail. The MIP microparticles could be packed into a solid phase extraction column for removing the target molecule in water efficiently, and the molecule could easily be enriched by 40 times. The interaction of the functional monomer and template was studied by the calculation method, giving a more clear understanding of the recognition behaviours of the imprinted polymers. The strategy could be extended not only to prepare highly specific MIPs for other small phosphoric molecules, but also for biomolecules e.g. phosphorylated peptides or proteins.

A novel strategy was developed for preparing highly selective molecularly imprinted polymers using 3-aminopropyltriethoxysilane as both a functional monomer and catalyst.     

A convenient separation method for di(2-ethylhexyl)phthalate by novel superparamagnetic molecularly imprinted polymers

Through a surface molecular imprinting technique and coating superparamagnetic Fe₃O₄ nanoparticles with molecularly imprinted polymers (MIPs), a novel magnetic molecularly imprinted polymer (MMIP) was successfully fabricated for the convenient separation of di(2-ethylhexyl)phthalate (DEHP) with methacrylic acid as functional monomer, ethylene glycol dimethacrylate as cross linker and 2,2-azobis(isobutyronitrile) as initiator. A magnetic non-molecularly imprinted polymer (MNIP) was also prepared for comparison purposes. The morphology structure and the magnetic properties of MMIP were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectrometry (FT-IR), X-ray diffraction, vibrating sample magnetometry (VSM) and thermo gravimetric analysis (TGA). The adsorption properties of MMIP and MNIP were investigated by static and dynamic adsorption experiments. The results show that the diameter of the synthesized MMIP microspheres is about 300–500 nm with good dispersibility in solvent. The prepared MMIP shows superparamagnetic properties with the maximum saturation magnetic intensity of 43.97 emu g⁻¹, and it can be conveniently separated using an external magnetic field. Compared with MNIP, MMIP has a higher adsorption capacity and better adsorption selectivity for DEHP, and the imprinting factor reaches 3.012. The regeneration adsorption experiment illuminates that the novel MMIP can be reused with good separation efficiency.

Through surface molecular imprinting technique and coating superparamagnetic Fe₃O₄ nanoparticles with molecularly imprinted polymers, a novel MMIP was successfully fabricated for the convenient separation of DEHP.     

Synthesis,characterization, and evaluation of selective molecularly imprinted polymers for the fast determination of synthetic cathinones

As a kind of new psychoactive substance (NPS), synthetic cathinones have drawn great worldwide attention. In this study, molecularly imprinted polymers (MIPs), as adsorbents for the extraction and determination of 4-methyldimethcathinone (4-MDMC), were first synthesized by coprecipitation polymerization. The physicochemical analyses of MIPs were successfully performed by XRD, FTIR, FESEM and TGA techniques. Furthermore, rebinding properties of temperature and pH dependence, and selectivity and reusability tests for MIPs and non-imprinted polymers (NIPs) were performed using an ultraviolet-visible spectrometer (UV-vis). The obtained results indicate that the imprinting efficiency has strong dependence on temperature and pH, and the optimal adsorption for targets is achieved under the condition of 318 K and pH = 6.0. This means that the combination between the polymers and 4-MDMC is a strong spontaneous and endothermic process. Compared with NIPs, MIPs exhibit prominent adsorption capacity (Q_e = 9.77 mg g⁻¹, 318 K). The selectivity coefficients (k) of MIPs for 4-MDMC, methylenedioxypentedrone (βk-MBDP), 4-ethylmethcathinone (4-EMC), methoxetamine (MXE) and tetrahydrofuranylfentanyl (THF-F) were found to be 1.70, 3.49, 7.14 and 5.82, respectively. Moreover, it was found that the adsorption equilibrium was achieved within 30 min. The aim of this work is the simple synthesis of MIPs and the optimal performance of the molecular recognition of 4-MDMC. Moreover, the synthesized MIPs can be easily regenerated and repeatedly used with negligible loss of efficiency (only 9.94% loss after six times adsorption–desorption tests). Satisfying recoveries in the range of 69.3–78.9% indicate that MIPs have good applicability for analyte removal from urine samples. Ultimately, this material shows great promise for the rapid extraction and separation of synthetic cathinones, which are dissolved in the liquid for the field of criminal sciences.

Molecularly imprinted polymers, as an adsorbent for extraction and selective recognition of 4-methyldimethcathinone, were firstly synthesized through coprecipitation polymerization.     

A facile synthesis of molecularly imprinted polymers and their properties as electrochemical sensors for ethyl carbamate analysis

New molecularly imprinted polymers (MIPs), which exhibit specific recognition of ethyl carbamate (EC) have been synthesized and studied. In this process, EC was the template molecule and β-cyclodextrin derivatives were employed as functional monomers in the molecular imprinting technique (MIT). An EC molecularly imprinted sensor (EC-MIS) was prepared by using MIT surface modification. The EC-MIS was characterized by cyclic voltammetry, electrochemical impedance spectroscopy and differential pulse voltammetry. EC detection performance, binding parameters and dynamics mechanism were investigated. The result showed that the synthetic route designed was appropriate and that new MIP and EC-MIS were successfully prepared. The EC-MIS exhibited a good molecular recognition of EC. A linear relationship between current and EC concentration was observed using cyclic voltammetry and the detection limit was 5.86 μg L⁻¹. The binding constant (K = 4.75 × 10⁶ L mol⁻¹) between EC and the EC-MIS, as well as, the number of binding sites (n = 1.48) has been determined. The EC-MIS recognition mechanism for the EC is a two-step process. The sensor was applied for the determination of EC in Chinese yellow wines, and the results were in good agreement with the gas chromatography-mass spectrometry (GC-MS) method.

An ethyl carbamate (EC) molecularly imprinted sensor (EC-MIS) has been prepared. The molecular recognition properties of EC were investigated, the binding parameters determined, and the dynamic mechanism of EC-MIS recognizing EC explored.     

生物可降解分子印迹聚合物的制备及评价

背景：交联剂是支撑分子印迹聚合物骨架的主要单元,分子印迹聚合物是否生物友好与交联剂的性能密不可分,但目前常用交联剂的生物相容性和生物降解性还不明确。 目的：制备新型生物可降解分子印迹聚合物,分析其吸附性能和可降解性能。 方法：以丙烯酰化的聚ε-己内酯为交联剂,以丙烯酸为功能单体,采用紫外光引发聚合法制备茶碱分子印迹聚合物,通过等温吸附、Scatchard分析和动力学曲线研究其吸附能力,在模拟人体生理环境体系中进行体外降解实验。 结果与结论：等温吸附曲线表明茶碱分子印迹聚合物和非分子印迹聚合物对模板分子茶碱均有吸附能力,但茶碱分子印迹聚合物的吸附量显著高于非分子印迹聚合物。茶碱分子印迹聚合物对茶碱的载药量为1.54%,包封率为12.48%,茶碱分子印迹聚合物和聚ε-己内酯二醇在观察时间内的体外降解率分别为6.60%和1.33%。制备的分子印迹聚合物不仅对目标分子有特异的吸附性能,而且具有良好的生物降解性能,可在模拟人体环境中进行降解。     

Molecularly imprinted polymers for selective adsorption of quinoline: theoretical and experimental studies

The effects of solvent on the synthesis of molecularly imprinted polymers (MIPs) for the selective adsorption of quinoline were evaluated in this work. The MIPs were synthesized by the “bulk” method using the quinoline molecule (IQ) as a template in different solvents, such as toluene (MIPT) and chloroform (MIPC). The adsorbents were characterized by thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), and N₂ adsorption/desorption measurements. The influences of time, adsorbate concentration, and temperature on the adsorption of quinoline by MIPT and MIPC were evaluated. Maximum adsorption capacities (q_e) of 35.23 and 24.10 mg g⁻¹ were obtained for MIPT and MIPC, respectively. Thermodynamic studies indicate that occur physisorption and a spontaneous process (Δ_adsG° < 0) entropically directed. Finally, the highest selectivity and reusability of MIPC for quinoline adsorption was ascribed to the better interaction between the chloroform and monomer, which favors the formation of porous adsorbents with higher numbers of adsorption sites.

Molecularly imprinted polymers synthesized by a one-pot synthesis absorb quinoline efficiently and selectively.     

Fast quantification of fluoroquinolones in environmental water samples using molecularly imprinted polymers coupled with internal extractive electrospray ionization mass spectrometry

In this study, a facile method based on molecularly imprinted polymers (MIPs) combined with internal extractive electrospray ionization tandem mass spectrometry (iEESI-MS/MS) was developed for the quantitative analysis of fluoroquinolones (FQs) in environmental water samples. FQ molecules in water samples were captured by the MIPs, which was retained on a 0.22 μm syringe filter. Then, an electrospray solution selected as the elution solution was employed to extract the FQs from the MIPs, getting an eluate of FQs for mass spectrometric interrogation. Under the optimized experimental conditions, low limits of detection (LODs, 0.015–0.026 μg L⁻¹), with relative standard deviations (RSDs) less than 8.81% (n = 6) were obtained. The present method also provides good recoveries (91.14–103.60%) with acceptable precision (RSDs < 6.18%) and have no serious matrix effects for environmental water samples. The experimental results demonstrated that MIPs-iEESI-MS/MS has advantages including easy use, high speed (less than 3 min per sample) and high sensitivity for the analysis of FQs in environmental water samples, showing potential application in environmental science and water safety control.

A simple, fast and high-sensitivity method for quantification of fluoroquinolones in environmental water samples using MIPs-iEESI-MS.     

Magnetic surface molecularly imprinted poly(3-aminophenylboronic acid) for selective capture and determination of diethylstilbestrol

Diethylstilbestrol (DES) is considered a representative example of an exogenous endocrine disrupting compound (EDC). It can retard development in infants, lead to serious metabolic regulation disorders, and even result in distortion and cancer in the reproductive system. Therefore, achieving rapid and accurate analysis of trace amounts of DES in complex environments is of great importance to human health and for environmental protection. Novel magnetic molecularly imprinted polymers (MIPs) with excellent molecular recognition ability and super water-compatibility were developed for the selective capture of DES in water samples. Fe₃O₄@SiO₂ magnetic nanoparticles (NPs) were synthesized and used as support cores. Molecularly imprinted poly(3-aminophenylboronic acid) (poly(APBA)), synthesized on magnetic cores based on a surface-imprinting strategy, can preferentially bind DES molecules in water samples. The magnetic core–shell MIPs (denoted as Fe₃O₄@SiO₂@APBA/MIPs) exhibited high binding capacity and favorable recognition specificity for DES in water. The adsorption kinetics and experimental isotherm data of DES on magnetic MIPs can be well described by the pseudo-second-order kinetic model and the Langmuir isotherm, respectively. The imprinted nanoparticles were subjected to magnetic solid-phase extraction (MSPE) of DES from water samples. The DES content in the samples was determined by high-performance liquid chromatography (HPLC). The peak area increased linearly with increasing DES concentration over the range 0.08–150 μg L⁻¹, with a detection limit of 0.03 μg L⁻¹. The recoveries for spiked lake water samples were in the range 97.1–103.2%, with relative standard deviation (RSD) of 2.8–4.3% (n = 6).

Imprinted poly(APBA) nanoshell on Fe₃O₄@SiO₂ surface was first synthesized and used for MSPE of diethylstilbestrol followed by HPLC determination.     

Drug-loaded dual targeting graphene oxide-based molecularly imprinted composite and recognition of carcino-embryonic antigen

Despite extensive research on functional graphene oxide for anticancer drug delivery, the sensitivity of traditional protein targeting ligands to the environment limits the practical applications of targeted drug delivery. A unique molecularly imprinted magnetic graphene oxide was used as a novel drug delivery system for the treatment of tumors. Molecularly imprinted polymers (MIPs) synthesized by molecular imprinting technology have the advantages of good stability against chemical and enzymatic attacks, high specificity for a target template, and resistance to harsh environments. In our work, the MIP was used for specificity to tumor cells with carcino-embryonic (CEA) tumor markers as the template, and dopamine as the functional monomer was grafted on boronic acid-functionalized magnetic graphene oxide. The structure of the nanoparticles was optimized and characterized in detail by vibrating sample magnetometry, X-ray diffraction analysis, UV-vis spectroscopy, and flow cytometry. The prepared polymer has magnetic properties, specific recognition to CEA, biocompatibility and pH sensitivity for drug delivery. Cell culture research was carried out on the tumor cells and normal cells. The composites exhibited dual targeting properties that not only magnetically target but also specifically increase the drug cytotoxicity to the tumor cells by selectively binding to CEA. On the basis of these results, this study developed a novel approach for targeting tumor cells for drug delivery without needing to modify the protein ligand.

In the research we designed a CEA-molecularly imprinted polymers using molecular imprinting technique with CEA tumor marker as template, boronic acid functionalized MGO as substrate for dual targeted delivery of drug to tumor cells.     

Preparation of monoethyl fumarate-based molecularly imprinted polymers and their application as a solid-phase extraction sorbent for the separation of scopolamine from tropane alkaloids

Molecularly imprinted polymers (MIPs) prepared using conventional functional monomers exhibit poor specific extraction of scopolamine from tropane alkaloids, which hinders their application in separation and purification. In this paper, a novel molecularly imprinted polymer (MIP) was prepared by precipitation polymerization using scopolamine as the template, monoethyl fumarate (MFMA) as a functional monomer, and ethylene dimethacrylate (EGDMA) as a cross-linker. The advantages of the supercritical fluid technology for the removal of the template were verified by comparing the efficiency of the swelling method and the Soxhlet extraction method. The prepared MFMA-based MIPs (MFMA-MIPs) showed a high adsorption capacity (49.75 mg g⁻¹) and high selectivity toward scopolamine with a selectivity coefficient of 3.5. ¹H NMR spectroscopy was performed to demonstrate the interactions between the two functional groups of the functional monomer and the template. Lastly, MFMA-MIPs were used as solid phase extraction (SPE) sorbents for scopolamine analysis. It was found that 97.0–107.0% of the template had been extracted using the SPE column from the complex of scopolamine, atropine and anisodamine. The mean recoveries of scopolamine from plant samples were 96.0–106.0% using the established method, which showed a good linearity in the range of 8.0–4.0 × 10⁴ μg L⁻¹. The results showed that MFMA-MIPs could be applied for the separation of scopolamine from tropane alkaloids.

Monoethyl fumarate with two functional groups was introduced to prepare a MIP for the separation of scopolamine from tropane alkaloids.     

A novel fluorescent functional monomer as the recognition element in core–shell imprinted sensors responding to concentration of 2,4,6-trichlorophenol

We have demonstrated a fluorescent functional monomer instead of the traditional functional monomers for molecularly imprinted sensors. The sensors were firstly used to selectively detect 2,4,6-trichlorophenol (2,4,6-TCP) by solid fluorescence detection without a dispersion solution. Moreover, the selectivity and anti-interference ability of the SiO₂@dye-FMIPs sensor meet the requirements of a fluorescent sensor. The novel fluorescent monomer introduced into MIP is no longer just a fluorophore without recognizing ability. The fluorescence intensity of SiO₂@dye-FMIPs showed a linear response to 2,4,6-TCP concentration in the range of 0–100 nM with a detection limit of 0.0534 nM. We could also demonstrate that such a system can not only get rid of the confines of traditional functional monomers and detection manner, but also improved the applications of MIPs sensors in sensing systems.

We have demonstrated a molecularly imprinted sensor with a fluorescent functional monomer instead of the traditional functional monomers to detect 2,4,6-TCP.     

A novel molecularly imprinted electrochemiluminescence sensor based on cobalt nitride nanoarray electrode for the sensitive detection of bisphenol S

A substitute for bisphenol A (BPA), bisphenol S (BPS) has endocrine disruptive and toxic effects and could pose potential risk on human health and the environment. Herein, we fabricated a sensitive molecularly imprinted electrochemiluminescence (MIECL) sensor for the determination of BPS. CoN nanoarray with outstanding electrical conductivity was prepared and it directly served as the sensor platform. Especially, due to the high surface area of the porous CoN nanoarray, the ECL probe of Ru(bpy)₃²⁺ could be absorbed on the electrode. By means of the cation exchange of Nafion membrane and utilizing tripropylamine (TPrA) as co-reactant, boosted ECL signals were obtained. Meanwhile, by combining with molecularly imprinted polymers (MIPs), the constructed sensor achieved specific recognition of BPS. On the basis of the superior properties of the CoN nanoarray-based electrode, the ECL signal of the proposed sensor was linearly proportional to the BPS concentration from 2.4 × 10⁻⁹ to 5.0 × 10⁻⁵ mol L⁻¹ (R² = 0.9965) with a low limit of detection (LOD) of 8.1 × 10⁻¹⁰ mol L⁻¹ (S/N = 3). To test the accuracy of the proposed method, the HPLC method was adopted to analyze drinking water samples as a comparison. The t-test result proved that discrepancies between HPLC analysis and the method using the fabricated MIECL sensor were acceptable. The developed MIECL sensor with the sensitive, selective, reproducible, and stable analytical performance provides a potential pathway for the detection of BPS and other BPA substitutes in drinking water samples.

Sensitive molecularly imprinted ECL sensor for the determination of BPS based on the CoN nanoarray electrode directly used as the ECL sensing platform was fabricated for the first time.     

Determination of sialic acid in serum samples by dispersive solid-phase extraction based on boronate-affinity magnetic hollow molecularly imprinted polymer sorbent

Boronate-affinity magnetic hollow molecularly imprinted polymers (B-MhMIPs) were prepared with sialic acid (SA) as the template, 3-aminophenylboronic acid (APBA) as the functional monomer and glycidilmethacrylate (GMA) as the co-monomer to chemisorb Fe₃O₄ nanoparticles. Furthermore, the hollow structure made the nanoparticles have more binding sites at both internal and external surfaces, which can facilitate the removal of template molecules from polymers and enhance the adsorption abilities towards SA. After optimizing, the adsorption pH was controlled at 4.0, and this was different from most cis-diol-containing compounds. Under the optimal conditions, the limit of detection for SA was 0.025 μg mL⁻¹ (n = 3). This method was applied to analyze serum samples with different spiked levels, and the recoveries of the SA were in the range of 70.9–106.2%. These results confirmed the superiority of the B-MhMIPs for selective and efficient enrichment of trace SA from complex matrices.

Boronate-affinity magnetic hollow molecularly imprinted polymers were prepared with sialic acid (SA) as a template to selectively extract SA from serum samples coupled with HPLC-UV.     

PEGylation of protein-imprinted nanocomposites sandwiching CdTe quantum dots with enhanced fluorescence sensing selectivity

Fluorescent sensors combining the selective recognition of protein molecularly imprinted polymers (MIPs) and the fluorescent sensing of quantum dots (QDs) have been studied considerably, but their fluorescence sensing selectivity for the target proteins remains to be increased. Herein, we propose a strategy for increasing the sensing selectivity by post-imprinting PEGylation of surface protein-imprinted nanocomposites with embedded QDs. With bovine hemoglobin (BHb) as a model protein template, protein MIP nanolayers were anchored over the CdTe QD decorated SiO₂ nanoparticles by the sol–gel process using aminopropyltriethoxy silane and tetraethoxysilicane. PEG chains were then grafted onto the surface of the imprinted nanostructures via the nucleophilic reaction of the surface amine groups with N-hydroxysuccinimide ester-terminal methoxy-PEG, followed by template removal. The resultant PEGylated sensors showed significantly improved aqueous dispersion stability compared with the non-PEGylated controls. More importantly, such PEGylation greatly increased the fluorescence response selectivity, with the Stern–Volmer equation based imprinting factor increasing from 2.7 to 5.4. The PEGylated sensors were applied to determine BHb in bovine serum samples with satisfactory recoveries at three spiking levels ranging from 94.3 to 103.7%, indicating their potential application in real samples.

PEGylated CdTe quantum dots containing protein-imprinted nanocomposites showing enhanced fluorescence sensing selectivity.     

Evaluation of matrices containing molecularly imprinted polymers in the enantioselective-controlled delivery of beta-blockers.

Granules and beads of methacrylic acid (MAA) and granules of N-acryloyl-alanine polymer (NAA) were produced using ethylene glycol dimethacrylate as cross-linking monomer either by bulk (in the case of granules) or suspension (in the case of beads) polymerization. Either R- or S-propranolol, were used as an imprint molecule, acting as a template, with a view to conferring enantioselectivity of release upon the polymer. The molecularly imprinted polymers (MIPs) or nonMIPs (control) were formulated with racemic propranolol and other excipients and compressed to form matrix tablets. Enantioselective release of propranolol in vitro was monitored using a stereoselective HPLC assay. The influence of the method of polymer synthesis, drug: polymer ratio, pH and temperature on the release of the two enantiomers was determined. Stereoselectivity of release was identified in tablets containing either MAA or NAA granules or MAA beads, with the latter showing the greatest differences between enantiomers. Release of the enantiomer used as the print was always faster than the release of the nonprint enantiomer. In the case of S-propranolol-MIP bead matrices composed of MAA, greater differences in the release of enantiomers could be promoted by increasing the polymer: drug ratio of the tablet. Differences in the release rate of the two propranolol enantiomers was still apparent as the pH was varied between 3 and 7.4 and when the temperature was decreased from 37 to 25 degrees C. S-Propranolol-MIP bead matrices demonstrated cross-reactivities of stereoselective dissolution for enantiomers of pindolol and oxprenolol, both of which have structural similarities to the imprint molecule. It is concluded that polymers of this type may have great potential in controlling, via means of formulation, the release of drug eutomer whilst enhancing retention of distomer in the dosage form.