Development and characterization of molecularly imprinted polymers for controlled release of citalopram

In this work, the use of molecularly imprinted polymers (MIPs) for citalolpram as anti-depressant drug was studied. Imprinted polymers were prepared from methacrylic acid (MAA; functional monomer), ethylene glycol dimethacrylate (EGDMA; cross-linker), and citalopram (as a drug template) using bulk polymerization method. The polymeric devices were further characterized by FT-IR, thermogravimetric analysis, scanning electron microscopy, and binding experiments. The dissolution media employed in controlled release studies were hydrochloric acid at the pH level of 4.3 and phosphate buffers, at pH levels of 7.2 and 10.1, maintained at 37.0 and 25.0 ± 0.5°C. Results showed the ability of MIP polymers to control the release of citalopram. In all cases, the imprinted polymers showed a higher affinity for citalopram and a slower release rate than the nonimprinted polymers. At the pH level of 4.3 and at the temperature of 25°C, slower release of citalopram imprinted polymer occurred.     

Preparation and characterization of molecularly imprinted poly(hydroxyethyl methacrylate) microspheres for sustained release of gatifloxacin

Molecularly imprinted poly(hydroxyethyl methacrylate) microspheres (PHEMA MIPMs) were prepared via precipitation polymerization in this article, using gatifloxacin (GFLX), hydroxyethyl methacrylate (HEMA), and ethylene glycol dimethacrylate (EGDMA) as template molecule, functional monomer and cross-linker, respectively. The effects of reaction medium, initial total monomers, cross-linker and molecular imprinting on the polymerization were investigated systematically. The interaction between GFLX and HEMA in pre-solution was studied by UV–Visible spectrophotometer, both size and morphology of products were characterized by a scanning electron microscope. When the total initial monomer concentration was 1 vol%, EGDMA content was 70 mol%, a group of uniform PHEMA MIPMs were prepared at different GFLX/MAA molar ratios, with diameter range from 2.06 ± 0.07 to 2.82 ± 0.20 μm. The results of drug loading and in vitro release experiments demonstrated that PHEMA MIPMs could achieve a higher GFLX loading content and a more acceptable sustained release than non-imprinted ones.     

Development of molecularly imprinted polymer as sustain release drug carrier for propranolol HCL

Applications of molecularly imprinted polymer (MIPs), is rapidly increasing, especially in the drug delivery field. Molecularly imprinted polymers are the molecular traps, which can entrap the specific molecule and also control its release. Polymer complexes were prepared with and without propranolol HCl as templates, MAA (methacrylic acid) as monomer and EGDMA (ethyleneglycol dimethacrylate) as crosslinker by solvent polymerization technique. Drug release pattern from these polymer complexes were compared and maximum drug release in 12?h was consider to optimize the ratio of MAA and EGDMA. Since, the maximum propranolol HCl release from polymer complex was low (62.15%) in optimized batch, inclusion complex of drug with β-cyclodextrin were prepared for the higher drug release (80.32%). The selected polymer complexes were treated with methanol for complete removal of the drug to form MIPs. These MIPs were reloaded with the drug and subjected for drug release. The release patterns from reloaded MIP’s were observed to be slightly quicker than their corresponding MIP’s.     

Development of a pH-responsive imprinted polymer for diclofenac and study of its binding properties in organic and aqueous media

Three different molecularly imprinted polymers (MIPs) for drug delivery of diclofenac in gastrointestinal tract were synthesized employing bulk polymerization method and their binding and release properties were studied in different pH values. Methacrylic acid (MAA), methacrylamide (MAAM) and 4-vinyl pyridine (4VP) were tested as functional monomers and ethylene glycole dimethacrylate (EDMA) was used as a cross-linker monomer in polymeric feed. Binding properties and imprinting factor (IF) of MIPs were studied in comparison with their non-imprinted ones (Blank) in organic and aqueous media. Diclofenac release in aqueous solvents at pH values of 1.5, 6.0 and 8.0, simulating gastrointestinal fluids, were also studied. The results indicated the specific binding of diclofenac to imprinted polymers. Duo to the stronger non-specific bounds in aqueous solutions, IF values decreased in water compared to acetonitrile as an organic medium. Our results proved that all polymers represented pH-responsive diclofenac delivery at above conditions. The data showed that imprinted polymer, prepared by MAA had superior properties, in comparison with other polymers, for minimum release (14%) of drug in gastric acid and maximum release (90%) in basic condition. The results indicated that diclofenac imprinted polymer could be used as a pH-responsive matrix in preparation of a new drug delivery system for diclofenac.     

Development of a pH-responsive imprinted polymer for diclofenac and study of its binding properties in organic and aqueous media

Three different molecularly imprinted polymers (MIPs) for drug delivery of diclofenac in gastrointestinal tract were synthesized employing bulk polymerization method and their binding and release properties were studied in different pH values. Methacrylic acid (MAA), methacrylamide (MAAM) and 4-vinyl pyridine (4VP) were tested as functional monomers and ethylene glycole dimethacrylate (EDMA) was used as a cross-linker monomer in polymeric feed. Binding properties and imprinting factor (IF) of MIPs were studied in comparison with their non-imprinted ones (Blank) in organic and aqueous media. Diclofenac release in aqueous solvents at pH values of 1.5, 6.0 and 8.0, simulating gastrointestinal fluids, were also studied. The results indicated the specific binding of diclofenac to imprinted polymers. Duo to the stronger non-specific bounds in aqueous solutions, IF values decreased in water compared to acetonitrile as an organic medium. Our results proved that all polymers represented pH-responsive diclofenac delivery at above conditions. The data showed that imprinted polymer, prepared by MAA had superior properties, in comparison with other polymers, for minimum release (14%) of drug in gastric acid and maximum release (90%) in basic condition. The results indicated that diclofenac imprinted polymer could be used as a pH-responsive matrix in preparation of a new drug delivery system for diclofenac.     

Design of size-tunable molecularly imprinted polymer for selective adsorption of acetaminophen

Pharmaceutical and personal care products are a broad and diverse group of biologically active compounds which are widely used and unregulated suspected carcinogens. In this study, the fabrication of molecularly imprinting polymer (MIP) particles by precipitation polymerisation were developed to selectively and rapidly capture acetaminophen, a commonly used analgesic and antipyretic drug, by hydrogen and hydrophobic bondings. Methacrylic acid, 3-(trimethoxysilyl) propyl methacrylate and 2, 2′-azobis-isobutyronitrile were utilised as the functional monomer, cross-linker and initiator. Acetonitrile was found to be the optimised porogen to obtain imprinted polymers with surface area and pore size of 447.2 m²/g and 3.35 nm. By adjusting the ratio of cross-linker and functional monomer, the particle size of MIPs changed from 177 to 2782 nm when the ratio increased from 0.43 to 12.8. In addition, the adsorption equilibrium of acetaminophen by MIPs can be reached within the first 30 min because of the surface imprinting characteristics and small particle sizes. In addition, the maximum adsorption capacity of acetaminophen and the adsorption constant, well fitted by Langmuir equation, were 0.35 mg/g and 0.045 L/mg. In addition, the MIPs exhibited the excellent selectivity to acetaminophen. The high surface area and adsorption capacity and excellent selectivity make MIPs an ideal tailor-made green material and can open the door to develop the novel technology for adsorption and removal of pharmaceutical and personal care products in the environment.     

运用电化学方法制备分子印迹聚合物膜

运用电化学方法制备了分子印迹聚合物。其制备方法具有速度快、直接成膜等优点。该膜对其模板分子具有极好的结合性能。     

Preparation of molecularly imprinted polymers for the detection of aromatic hydrocarbons

In this study, the molecularly imprinted polymers (MIPs) are designed to improve their sensitivity and selectivity for specific aromatic hydrocarbons such as benzene, toluene, and xylene isomers. The MIPs based on methyl acrylate (MA) monomer are prepared using toluene and ethylene glycol dimetacrylate (EGDMA) as a template and a cross linking agent, respectively. The binding sites on the MIPs are characterized by using Fourier transform infrared spectrometry (FT-IR), nitrogen adsorption isotherms, and transmission electron microscopy (TEM). The selective behaviors of the MIPs are evaluated by their adsorption properties on a gravimetric apparatus. It is found that the performance is strongly influenced by the composition ratios of cross-linker, functional monomer, and template molecule. The molecular recognition ability can be assessed on the basis of an imprinting effect. The results indicate that the prepared MIPs can be used for the aromatic hydrocarbon sensor materials with high sensitivity and selectivity.     

单一结合位点分子印迹聚合物的合成及性能

采用分子自组装印迹技术在光引发条件下制备了以(S)-布洛芬为模板分子,α-甲基丙烯酸为功能单体的分子印迹聚合物。通过红外对聚合物的结构进行了表征。透射电镜结果表明,交联剂用量对印迹聚合物的形貌特征具有显著的影响。同时结合Scatchard分析研究了印迹聚合物的吸附性能及选择性识别能力,表明印迹聚合物特异性吸附容量为41μmol/g,印迹指数为2.28,对(S)-布洛芬形成单一结合位点,且表现出明显的吸附选择性。     

Preparation of MRI-visible gadolinium methacrylate nanoparticles with low cytotoxicity and high magnetic relaxivity

A new convenient and easy-scalable one-step synthetic strategy to achieve metal-containing polymer nanoparticles for applications as magnetic resonance imaging contrast agent is reported. In this study, a novel contrast agent based on poly(gadolinium methacrylate) (poly(Gd(MAA)₃)) nanoparticles was prepared by one-step aqueous dispersion polymerization of gadolinium methacrylate monomer (Gd(MAA)₃), whereby stable particles were obtained due to the association of Gd^III with the polymer carboxylate anions, which provided latent crosslinking of the polymer nanoparticles without the addition of further crosslinking reagents. The morphology and final composition of the corresponding nanoparticles was thoroughly characterized and their cytotoxicity as well as their potential use in MRI was evaluated in vitro on HEK 293T cells by using the CCK-8 assay. The presented results demonstrated, that the poly(Gd(MAA)₃) nanoparticles had a spherical morphology with mesoporous substructure, a sufficiently low cytotoxicity and an exceptionally high longitudinal relaxivity of r ₁ = 12.613 mM^?1 s^?1, making these nanoparticles excellent candidates for in vivo imaging systems. Herein described poly(Gd(MAA)₃) nanoparticles can be valuable in a wide range of biomedical applications with simultaneous bioconjugation, drug delivery as well as imaging capabilities for the early detection of lesions of the brain and the central nervous system, for assessing cardiac function, and for detecting tumors.     

农药对硫磷分子印迹聚合物合成及亲和性评价

对硫磷为模板分子,甲基丙烯酸(MAA)为功能单体,乙二醇二甲基丙烯酸酯(EGDMA)为交联剂,偶氮二异丁腈(AIBN)为引发剂,热引发沉淀聚合法合成对硫磷分子印迹聚合物(MIP)。通过计算机模拟和紫外分析阐述模板与功能单体的分子间作用;通过电镜观察和平衡吸附试验讨论引发剂用量与聚合物性质关系;通过吸附试验Scatchard分析测得最大吸附量为3.92μmol/g,平衡解离常数为91.7μmol/L,且具有较好的吸附特异性。该分子印迹聚合物性能优良,有望应用于环境中对硫磷的富集和检测。     

牺牲硅胶骨架法制备盐酸黄连素印迹聚合物及其性能研究

以盐酸黄连素（berberine-C1）为模板分子,硅胶为牺牲载体,甲基丙烯酸（MAA）或4-乙烯基吡啶（4-VP）、二甲基丙烯酸乙二醇酯（EDMA）及偶氮二异丁腈（AIBN）分别为功能单体、交联剂及引发剂制备了黄连素印迹聚合物。用光学显微镜观察了聚合物形貌,红外光谱（IR）研究了印迹聚合物（Mip）对模板分子的再结合...     

Extraction and purification of penicillin G from fermentation broth by water-compatible molecularly imprinted polymers

Highly selective molecularly imprinted polymer (MIP) was synthesized by using methacrylic acid as functional monomer, trimethylolpropane trimethacrylate as cross-linker, chloroform as porogen and penicillin G potassium as template molecule. These imprinted polymers were used as solid-phase extraction sorbent for the selective extraction of penicillin G from the fermentation broth samples. Various parameters affecting the extraction efficiency of the MIP particles such as; effects of pH, wash and eluent solutions were evaluated. Molecular recognition properties and selectivity of these MIPs were estimated and the obtained results revealed high affinity for the target antibiotic. Equilibrium binding experiments were done to assess the performance of the MIP relative to non imprinted polymer (NIP). After optimizing the extraction parameters in molecularly imprinted solid-phase extraction (MISPE), successful imprinting was confirmed by comparison of the recoveries from the fermentation broth, ranging between 24–26% (RSD 4.1–4.5%, n = 4) for the NIPs and 83–88% (RSD 3.1–3.4%, n = 4) for the MIPs.     

阿司匹林表面印迹微球的制备与药物缓释性能评价

采用表面印迹技术,选取γ-氨丙基三甲氧基硅烷(APTS)和甲基丙烯酰氯修饰的硅胶为载体,以阿司匹林(Asp)为模板分子,丙烯酰胺(AM)为功能单体,乙二醇二甲基丙烯酸酯(EDGMA)为交联剂,在乙腈溶液中合成了阿司匹林表面分子印迹聚合物微球(MIPs)和非印迹聚合物微球(NIPs)。通过紫外、红外光谱、扫描电镜、透射电镜、热重分析以及吸附实验进行了表征并进行了药物扩散实验。结果表明,MIPs平衡吸附量可达164.40μmol/g,对苯甲酸(BA)和水杨酸(SA)的分离因子达到3.15和3.32,有很好的热稳定性和选择性吸附能力;MIPs持续释药时间是NIPs的2.6倍,有很好的缓释效果和应用价值。     

Molecularly imprinted nanoparticles prepared by miniemulsion polymerization as selective receptors and new carriers for the sustained release of carbamazepine

Water-compatible imprinted nanoparticles were prepared for carbamazepine as a template and used for the selective extraction and controlled release of carbamazepine. Assay materials and drug delivery carriers were typically used in aqueous environments, so it is generally preferable to prepare solvent-free molecularly imprinted nanoparticles in water using the miniemulsion polymerization method. The present work investigates a bio-analytical strategy generically applicable to imprinted materials for molecular recognition studies, including equilibrium and non-equilibrium binding, and release experiments, increasing the knowledge of the molecular interactions between the template molecules and imprinted nanoparticles. The results showed that the imprinted nanoparticles exhibited a higher binding level and slower release rate than non-imprinted nanoparticles. The selectivity of imprinted nanoparticles for carbamazepine studied in comparison with an analogue compound, oxcarbazepine, the main metabolite of carbamazepine. The recovery and selectivity of carbamazepine in human serum was determined to be 100%, 1.7 times that of oxcarbazepine. The results indicated that carbamazepine-imprinted nanoparticles are appropriate for serum level determination of the drug in therapeutic range. The template to functional monomer ratio as a key factor controlling the recognition and release kinetic mechanism of imprinted nanoparticles is discussed. The imprinted nanoparticles prepared at the appropriate template to functional monomer mole ratio (2:8) exhibited the best drug affinity (5.1 times higher) and a slower drug release rate due to the interaction of carbamazepine with the imprinted cavities within the nanoparticles. Loaded imprinted nanoparticles as drug reservoirs were able to prolong carbamazepine release, in 1% wt sodium dodecyl sulfate aqueous solution, for more than 8 days.     

Preparation of N,N-p-phenylene bismethacryl amide as a novel cross-link agent for synthesis and characterization of the core–shell magnetic molecularly imprinted polymer nanoparticles

Novel magnetic molecularly imprinted nanoparticles (MMIPs) using N,N-p-phenylene bismethacryl amide as a cross linker and super paramagnetic core–shell nanoparticle as a supporter for use in controlled release were prepared by precipitation polymerization. Novel cross-linking agents were synthesized by the reaction of methacryloyl chloride with p-phenylenediamine. Then, the Fe₃O₄ nanoparticles were encapsulated with a SiO₂ shell and functionalized with –CH=CH₂ and MMIPs were further prepared by using methacrylic acid as a functional monomer, N,N-p-phenylene bismethacryl amide as a cross-linking agent and betamethasone as template. Magnetic non-MIPs were also prepared with the same synthesis procedure as with MMIPs only without the presence of the template. The obtained MMIPs were characterized by using transmission electron microscopy, Fourier transform infrared spectrum, X-ray diffraction, energy-dispersive X-ray spectroscopy, and the vibrating sample magnetometer. The performance of the MMIPs for the controlled release of betamethasone was assessed and results indicated that the magnetic MIPs also had potential applications in drug controlled release.     

Preparation and characterization of molecularly imprinted polymers for the selective separation of 2,4-dichlorophenoxyacetic acid

As a method of preparing ligand-selective cavities in a synthetic polymer matrix, molecular imprinting technique has been attracting significant interest from a large number of areas in chemistry and analytical sciences. In this study, molecularly imprinted polymers (MIPs) were prepared with styrene, 4-vinylpyridine (4-VPy), and divinylbenzene (DVB) for the separation of hazardous 2,4-dichlorophenoxyacetic acid (2,4-D), and the selectivity of MIPs as adsorbed 2,4-D and structurally similar materials was evaluated. The template was removed through the swelling process of toluene/ethanol, and the removal ratio was about 95–99%, respectively. MIPs synthesized in this study had good adsorption selectivity in the presence of other materials, although there was a difference of adsorption quantities (uptake) in the functional monomer (4-VPy contents) and the cross-linker (DVB contents). The results exhibit that the selectivity of MIPs was improved significantly by controlling the cross-linker. We expect that molecular imprinting technique will serve as a novel method for selective separation of specific materials in various fields, especially in the fields of environment and pharmaceutics.     

X-Ray Photoelectron Spectroscopy characterization of electrosynthesized poly(3-thiophene acetic acid) and its application in Molecularly Imprinted Polymers for atrazine

X-Ray Photoelectron Spectroscopy (XPS) was used to extensively investigate the chemical structure of electrosynthesized poly(3-thiophene acetic acid). The observation of the integrity of carboxylic functionalities upon polymerization, along with the strong affinity between monomer and the herbicide atrazine (At) evidenced by Nuclear Magnetic Resonance, prompted the exploitation of the application of the electrosynthesized polymer in the preparation of a Molecularly Imprinted Polymer (MIP) for At. Experimental conditions for film electrosynthesis in the presence of template (At) were selected. XPS spectroscopy was used also for the characterization of the imprinted film, evidencing the entrapment of the template in polymer matrix and the removal of most template upon washing. Moreover, XPS results about the use of a cross-linking agent (3,3-bithiophene) for prospective improvement of MIP structural integrity are illustrated.     

Monoclonal behavior of molecularly imprinted polymer nanoparticles in capillary electrochromatography

A new approach based on miniemulsion polymerization is demonstrated for synthesis of molecularly imprinted nanoparticles (MIP-NP; 30-150 nm) with "monoclonal" binding behavior. The performance of the MIP nanoparticles is characterized with partial filling capillary electrochromatography, for the analysis of rac-propranolol, where (S)-propranolol is used as a template. In contrast to previous HPLC and CEC methods based on the use of MIPs, there is no apparent tailing for the enantiomer peaks, and baseline separation with 25,000-60,000 plate number is achieved. These effects are attributed to reduction of the MIP site heterogeneity by means of peripheral location of the core cross-linked NP and to MIP-binding sites with the same ordered radial orientation. This new MIP approach is based on the substitution of the functional monomers with a surfactant monomer, sodium N-undecenoyl glycinate (SUG) for improved inclusion in the MIP-NP structure and to the use of a miniemulsion in the MIP-NP synthesis. The feasibility of working primarily with aqueous electrolytes (10 mM phosphate with a 20% acetonitrile at pH 7) is attributable to the micellar character of the MIP-NPs, provided by the inclusion of the SUG monomers in the structure. To our knowledge this is the first example of "monoclonal" MIP-NPs incorporated in CEC separations of drug enantiomers.     

Computational approach to the rational design of molecularly imprinted polymers for voltammetric sensing of homovanillic acid

A methodology based on density functional theory calculations for the design of molecularly imprinted polymers (MIPs) is described. The method allows the rational choice of the most suitable monomer and polymerization solvent among a set of chemicals traditionally used in MIP formulations for the molecular imprinting of a given template. It is based on the comparison of the stabilization energies of the prepolymerization adducts between the template and different functional monomers. The effect of the polymerization solvent is included using the polarizable continuum model. A voltammetric sensor for homovanillic acid was constructed using different MIPs as recognition element, confirming that the solvent (toluene) and functional monomer (methacrylic acid) selected according to the theoretical predictions lead to the most efficient molecular recognition sensing phase. With the voltammetric sensor prepared using the MIP designed according to the theoretical predictions, a linear response for concentrations of homovanillic acid between 5 x 10(-8) and 1 x 10(-5) M can be obtained. The limit of detection is 7 x 10(-9) M. The selectivity obtained for homovanillic acid over other structurally related compounds buttresses the validity of this strategy of design.