Research status of molecularly imprinted hydrogel drug-loaded contact lenses / 中华实验眼科杂志

Traditional ophthalmic pharmaceutical preparations are mostly eye drops or eye ointments, which have the disadvantages of low efficiency and poor patient compliance in application.Drug-loaded contact lenses can overcome these shortcomings and have attracted much attention.Improving drug loading capacity and enhancing sustained-release performance of drug-loaded contact lenses are the main focus of research and development.In recent years, drug-loaded contact lenses made of molecularly imprinted hydrogel can significantly improve drug loading capacity and sustained-release performance, and have been widely studied.The application status of molecularly imprinted hydrogel drug-loaded contact lenses in the delivery of ophthalmic drugs, as well as the effects of various factors on drug loading capacity and sustained-release performance were reviewed in this article.

Progress on contact lens for extended ophthalmic drug delivery / 国际眼科杂志(Guoji Yanke Zazhi)

Conventional eye treatment formulation such as eye drops has shortcomings including low drug utilization and poor patient compliance. The contact lens(CL), well-known as visual correction lens, is considered to be a more promising ophthalmic drug delivery vehicle owing to its good biocompatibility, long-term wearing comfort, prolonged drug residence time and improved bioavailability. In order to improve the drug loading efficiency and prolong the release time, researchers have developed a variety of strategies to modify traditional CL, including the introduction of vitamin E molecular barrier, application of molecular imprinting technology of CL, increasing interactions between the drug and polymer matrix by introducing special genes, and incorporation of nanocarriers or drug-loaded polymer films. In this paper, the preparation methods and pros and cons of drug-loaded CL are reviewed. At last, the existing problems and future developments of CL as ophthalmic drug delivery carrier are briefly discussed.

Multi-template molecularly imprinted solid phase extraction and its application in the extraction and separation of multi-components from traditional Chinese medicine / 药学学报

Multi-template molecularly imprinted solid phase extraction not only has the advantages of high selectivity, large adsorption capacity, easy preparation, reuse and low environmental pollution, but also can realize the enrichment and separation of many kinds of compounds. It has attracted wide attention in the extraction and separation of traditional Chinese medicine components. This study summarizes the latest development of multi-template molecularly imprinted solid phase extraction. At the same time, based on the classification of active components of traditional Chinese medicine (flavonoids, alkaloids, phenylpropanol, terpenes, etc.), the latest application of multi-template molecular imprinting solid phase extraction in multi-component separation of traditional Chinese medicine was reviewed, with a view to better application of multi-template molecularly imprinted polymer in active multi-component extraction and separation of traditional Chinese medicine and provide reference for the material basic research of the efficacy of traditional Chinese medicine.

Preparation of morin-Cu2+ complex imprinted polymer and its application in solid phase extraction / 中草药

Objective: To prepare morin-Cu2+ complex imprinted polymer (CIP) and use the polymer to extract morin from mulberry branch. Methods: Morin-Cu2+ CIPs were prepared in water-methanol polar solvent in the presence of Cu2+, acrylamide as the functional monomer. The CIPs were used as the solid phase extraction sorbent for extracting morin from mulberry branch. Results: The prepared CIPs had specific and selective adsorption on morin, the maximum adsorption capacity was 82 μmol/g, which was much higher than that of the traditional imprinted polymers relying on hydrogen bond and non-imprinted polymers. The separation factors of CIPs to daidzein and catechin were 4.81 and 4.02, respectively. CIPs had a significant enrichment effect on morin in the composition of the mulberry branch solid phase extraction elution solution. Conclusion: Morin-Cu2+ CIPs are excellent material used for the separation and enrichment of morin, the material has good selective adsorption ability and environmental adaptability.

Preparation and application of curcumin molecularly imprinted composite membrane based on ATRP technique / 中草药

Objective: To prepare the molecularly imprinted composite membrane of curcumin by the atom transfer radical polymerization (ATRP) technique and develop a method for the separation and enrichment of curcumin in actual samples. Methods Curcumin MIM were prepared by thermal polymerization method using curcumin as template molecule, methylacrylic acid as functional monmers, cuprous chloride as catalyst, pentamethyldiethylenetriamine as ligand, and polyvinylidene fluoride as base membrane. The microstructure of MIM was investigated by SEM. The maximum adsorption and adsorption equilibrium time of MIM were investigated by static and dynamic adsorption experiment, and the selective penetration capacity was studied. The MIM as membrane material of osmotic device combined with HPLC was used for separation, enrichment and determination of curcumin in samples. Results The results showed that the prepared curcumin MIM had a regular distribution of pores and a uniform size. The maximum adsorption capacity was 3.81 mg/g, and the adsorption equilibrium could be achieved in 15 min. In the selective permeation process of ferulic acid, quercetin and curcumin, MIM had a high selective permeability to curcumin. The average recovery rates of curcumin in ginger, turmeric and curry were (94.100 ± 3.952)%, (98.300 ± 3.637)%, and (97.900 ± 3.133)%, respectively. The RSD was less than 4.2%. The limit of detection was 1.76 μg/kg. Conclusion The prepared MIM is a new material for strong selectivity, separation and enrichment of Chinese medicine curcumin with fast adsorption speed. At the same time, it also provides reference for chemical composition research of other Chinese materia medica.

Molecular imprinting technology and its application in terpenoids / 中国中药杂志

Molecular imprinting technology is widely used in the separation and analysis of compounds such as flavonoids, alkaloids and polyphenols, due to its high selectivity and specific recognition and so on. However, no much of attention has been paid to the terpenoids. This paper is aimed to not only review the effects of common synthetic elements such as functional monomers, cross-linking agents and porogens on the polymer properties, but also highlight the application of terpene molecular imprinting in solid phase extraction, sensor, membrane separation and chromatographic separation by means of statistical analysis of literature. Furthermore, the shortcomings and improvement directions are discussed.We believed that this paper could provide references for better applications of molecular imprinting techniques to the analysis of terpenoid compounds.

Fluorescence Carbon Dot-based Imprinted Polymer for Highly Selective Detection of Bovine Hemoglobin / 分析化学

A novel fluorescent imprinted polymer (CDs@ MIP) with selective recognition of hemoglobin was prepared by the sol-gel method using fluorescent carbon dots as the carrier material, 3-aminopropyltrieth-oxysilane as the functional monomer, tetraethoxysilane as the crosslinking agent and bovine hemoglobin as template molecule. The results of IR and scanning electron microscopy showed that the molecularly imprinted polymer was coated on the surface of fluorescent carbon dots. The CDs@ MIP showed selective recognition properties for bovine hemoglobin with an imprinting factor of 4. 60. Also the adsorption ability and specific recognition performance of CDs@ MIP were investigated, and it was found that the CDs@ MIP had high selectivity toward bovine hemoglobin, and the selection factors for ovalbumin, bovine serum albumin and human serum albumin were 4. 38, 4. 73 and 3. 66, respectively. Under the optimal conditions, the linear range of CDs@ MIP for bovine hemoglobin was 0. 1-10. 0 μmol/ L and the detection limit was 23. 0 nmol/ L. The CDs@ MIP was successfully used for the determination of bovine hemoglobin in bovine blood samples with recoveries of 99. 0％ -102. 5％ .

Determination of Levofloxacin in Pork by Molecularly Imprinted Solid Phase Extraction Spectroscopy / 分析化学

A printed polymer for selective identification of levofloxacin was synthesized on the surface of silica gel with levofloxacin as template molecule. The polymer was characterized by elemental analysis and infrared spectroscopy, and the properties of the polymer were determined by dynamic adsorption and selective adsorption. The results showed that the maximum adsorption capacity of the imprinted polymer was 56.33 mg/g and the imprinting factor was 2.62. The imprinted polymer was applied to quantitative analysis of levofloxacin with molecular imprinted solid phase extraction spectroscopy (SPES). The SPES was carried out in an elaborately designed device with which the interested analyte was extracted by the solid phase extraction medium and the diffuse reflectance spectrum was measured directly on the solid medium without elution. SPES has simplified the operation process and improved the sensitivity. The regression equation of the standard curve was A=0. 0496C+0. 2412, the correlation coefficient (R2) was 0. 9924, the linear range was 0. 25-9.0 mg/L,and the detection limit was 0.24 mg/L. The recoveries of determination of levofloxacin in Pork samples were 89.1%-92.0%, and the relative standard deviations (RSDs) of the three parallel tests were 3.4%-7.9%. Compared with the traditional enrichment and separation technique, this method developed here had some advantages such as miniaturization and integration, high sensitivity and selectivity, low cost, simple operation and rapid detection.

Preparation of Melamine Molecularly Imprinted Surface Plasmon Resonance Sensor and Its Analytical Application / 分析化学

The melamine molecular imprinted polymer ( MIP ) membrane immobiliZed on the surface of the surface plasmon resonance ( SPR) chip was prepared with allylcyanurate and ethylene glycol dimethacrylate as a functional monomer and cross-linker, respectively.Based on the ratio of the intercept to the slope of Langmuir equation for imprinted polymer, the association constant ( Kass ) of imprinted sites in the imprinted film to melamine was calculated to be 1.40 × 108 L/mol.The SPR sensor showed high selectivity to the template molecule melamine, and the best response was obtained at pH=7.5.The method showed good linearity in the melamine concentration range of 0.1-10.0 nmol/L ( R=0.9991 ).Based on a signal to noise ratio of 3, the detection limits of melamine were 62.6 pmol/L and 56.4 pmol/L for the milk and milk powder, respectively.The recoveries were 91.5% for milk and 92.0% for milk powder.These results suggest that SPR sensing combined with MIP film is a promising alternative method for detection of melamine.

Del fenotipo neuropsiquiátrico al cuidado clínico del síndrome de Angelman: descripción de siete casos / Neuropsychiatrie phenotype of Angelman syndrome and clinical care: report of seven cases

El síndrome de Angelman es un trastorno neurogenético debido a la falta o reducción en la expresión del gen UBE3A en el cromosoma 15, el cual codifica la proteína ubiquitina ligasa E3A, que tiene un papel integral en el desarrollo sinóptico y la plasticidad neuronal. Se manifiesta por retraso en el neurodesarrollo o discapacidad intelectual, comportamiento característico y epilepsia. Se describen las características clínicas de siete pacientes con deleción del cromosoma 15q11-13 y su manejo integral. Por la expectativa de vida, es importante conocer y manejar las comorbilidades de forma interdisciplinaria para lograr mejorar la calidad de vida de los afectados. Se realiza una revisión de la literatura sobre la aproximación integral al diagnóstico y cuidado clínico a largo plazo de los pacientes con síndrome de Angelman.

Angelman syndrome is a neurogenetic disorder caused by a lack or reduction of expression of UBE3A located within chromosome 15, which codes for ubiquitin protein ligase E3A, which has a key role in synaptic development and neural plasticity. Its main features are developmental delay/intellectual disability, lack of speech, a characteristic behavioural profile, and epilepsy. We describe clinical features and management of seven cases with 15q11-13 deletion. Due to their life expectancy, knowing and managing its comorbidities is crucial to improve their quality of life. We review the diagnosis and long-term clinical care of patients with Angelman syndrome.

Construction of the brain-targeting drug carrier through imprinting of nicotinic acetylcholine receptor α7 / 药学学报

In this study, a novel brain-targeting carrier was made via conformational epitope imprinting. Acrylamide and N,N'-methylene bisacrylamide was used as carrier materials and the N-terminal epitope of nicotinic acetylcholine receptor α7 (nAchR α7) was tested as a template molecule, and the polymer nanoparticles were obtained after polymerization and template removal. The nanoparticles were investigated by particle size analyzer and transmission electron microscopy (TEM). Their targeting capabilities were investigated with a cell uptake assay in vitro and fluorescence imaging in vivo. The results suggest that the nanoparticles had a small particle size (42.1±4.3 nm) with a homogeneous distribution, and good targeting properties in vitro and in vivo. We have made the molecularly imprinted polymer nanoparticles with brain targeting capability, which represents a new tool in the treatment of brain diseases.

An Insulin Molecularly Imprinted Electrochemical Sensor Based on Epitope Imprinting / 分析化学

A novel molecularly imprinted electrochemical sensor for direct detection of insulin was prepared based on epitope imprinting.C-Terminal polypeptide in insulin as template molecule was firstly self-assembled on the Au electrode.Then the molecularly imprinted polymer (MIP) was fabricated by electropolymerization with o-phenylenediamine (o-PD) as functional monomer on this Au electrode.After elution of template molecules by NaOH solution, the imprinting cavities were formed with the three-dimensional structure matched with the polypeptide in insulin molecules.The imprinting cavities could specifically recognize and rebind with insulin molecules.With K3[Fe(CN)6]/K4[Fe(CN)6] as a probe, the insulin was indirectly detected.There was a linear relationship between the response current and the insulin concentrations in the range of 1.0 × 10-14-5.0 × 10-13 mol/L, and the detection limit was 7.24×10-15 mol/L.The developed sensor exhibited good selectivity and stability, and could be applied to the determination of serum samples.

Contact lenses as drug controlled release systems: a narrative review / As lentes de contacto como sistema de libertação controlada de fármacos: uma revisão narrativa

ABSTRACT Topically applied therapy is the most common way to treat ocular diseases, however given the anatomical and physiological constraints of the eye, frequent dosing is required with possible repercussions in terms of patient compliance. Beyond refractive error correction, contact lenses (CLs) have, in the last few decades emerged as a potential ophthalmic drug controlled release system (DCRS). Extensive research is underway to understand how to best modify CLs to increase residence time and bioavailability of drugs within therapeutic levels on the ocular surface.These devices may simultaneously correct ametropia and have a role in managing ophthalmic disorders that can hinder CL wear such as dry eye, glaucoma, ocular allergy and cornea infection and injury. In this narrative review the authors explain how the ocular surface structures determine drug diffusion in the eye and summarize the strategies to enhance drug residence time and bioavailability. They synthesize findings and clinical applications of drug soaked CLs as DCRS combined with delivery diffusion barriers, incorporation of functional monomers, ion related controlled release, molecular imprinting, nanoparticles and layering. The authors draw conclusions about the impact of these novel ophthalmic agents delivery systems in improving drug transport in the target tissue and patient compliance, in reducing systemic absorption and undesired side effects, and discuss future perspectives.

RESUMO A forma mais frequente de aplicação terapêutica em oftalmologia consiste na instilação de gotas oculares, mas dadas as limitações anatómicas e fisiológicas do olho, é necessária dosagem frequente com possível repercussão na adesão do paciente à terapêutica. Nas últimas décadas, as lentes de contacto (CLs) têm surgido como um potencial sistema de libertação controlada de fármacos na superfície ocular (DCRS) para correção do erro refrativo. Está em curso uma extensa investigação para entender a melhor forma de modificar as CLs, de modo a aumentar o tempo de residência e a biodisponibilidade do medicamento na superfície ocular dentro de níveis terapêuticos. Ao corrigirem a ametropia, estes dispositivos poderão simultaneamente desempenhar um papel na gestão de perturbações oftalmológicas, tais como a síndrome do olho seco, glaucoma, alergia ocular e infecção corneana, que podem comprometer o porte seguro e confortável das CLs. Nesta revisão narrativa, os autores explicam como as estruturas da superfície ocular determinam a difusão de fármacos no olho e sintetizam as estratégias para aumentar a permanência e biodisponibilidade dos mesmos. Em seguida, apresentam os resultados e as aplicações clínicas das CLs embebidas em fármacos, como DCRS, através da incorporação de barreiras de difusão, de monómeros funcionais, da liberação controlada por iões, da impressão molecular, de nanopartículas e pelo processo camada sobre camada. Os autores concluem avaliando o impacto destes novos sistemas de entrega de agentes farmacológicos ao melhorar o seu transporte no tecido alvo, reduzindo a sua absorção sistémica e os seus efeitos colaterais indesejáveis, e discutem perspectivas futuras.

Preparation and application of aminophyllin electrochemical sensor based on molecularly imprinting technique / 军事医学

Objective To establish a method for detection of aminophylline in blood samples of preterm infants . Methods A molecularly imprinted electrochemical sensing film on the glassy carbon electrode surface was prepared by electropolymerization using aminophylline as the template molecule and pyrrole as the functional monomer in 0.2 mol/L HAc-NaAc buffer solution ( pH 4.0).The surface morphology and properties of molecularly imprinted sensing films were characterized by three dimensional laser scanning microscopy , differential pulse voltammetry ( DPV) and electrochemical impedance spectroscopy ( EIS) while the effects of scanning cycle number and incubation time were investigated by square wave voltammetry(SWV) method in 5 mmol/L K3[Fe(CN)6] -0.1 mol/L KCl solution.Results Under optimized experimental conditions ,the SWV peak current difference was linear to the negative logarithm of aminophylline concentration in the range from 1.0 ×10 -7 to 1.0 ×10 -3mol/L with a detection limit (S/N=3) of 0.5 ×10 -8mol/L.The recovery rate was 92.2% -101.4%.Also, the molecularly imprinted electrochemical sensor for aminophylline had good selectivity , stability and reproducibility .Conclusion The molecularly imprinted electrochemical sensor for aminophylline can be used for rapid and accurate detection of clinical blood concentrations of aminophylline molecules in preterm infants in the future .

Preparation of molecular imprinted polymers for solid-phase extraction of L-tetrahydropalmatine / 中草药

Objective: To prepare the molecularly imprinted polymer (MIPs) of L-tetrahydropalmatine (L-THP) by the molecular imprinting technique and study on solid-phase extraction. Methods: Using L-THP as template, methyl acrylic acid (MAA) as functional monmer, and ehtylene glycol dimethacrylate (EDMA) as a cross-linking agent to prepare the L-THP-MIPs. A test was conducted to investigate the selectivity and the specificity of solid-phase extraction. Results: The experiment showed that the MIPs had the specific adsorption to L-THP, but did not have the specific adsorption to corydaline the structural analogue with L-THP. Conclusion: The L-THP-MIPs have a good selectivity and the specificity of L-THP.

Application of isothermal titration calorimetry in molecular imprinting technique / 中国生化药物杂志

Molecular imprinting technique is a novel technology for preparing polymers with specific binding properties tosome specific molecules, and received widely attention in recent years.The article that was reviewed the applications of microcalorimetry in the molecular imprinting technique.The basic principle of microcalorimetry,characteristics and its advanced applications on evaluating imprinting effects of the molecularly imprinted polymers, screening of the monomers and the cross-linking agents, optimizing reaction conditions etc.were introduced.

New techniques of on-line biological sample processing and their application in the field of biopharmaceutical analysis

Biological sample pretreatment is an important step in biological sample analysis. Due to the diversity of biological matrices, the analysis of target substances in these samples presents significant challenges to sample processing. To meet these emerging demands on biopharmaceutical analysis, this paper summarizes several new techniques of on-line biological sample processing: solid phase extraction, solid phase micro-extraction, column switching, limited intake filler, molecularly imprinted solid phase extraction, tubular column, and micro-dialysis. We describe new developments, principles, and characteristics of these techniques, and the application of liquid chromatography-mass spectrometry (LC-MS) in biopharmaceutical analysis with these new techniques in on-line biological sample processing.

Preparation and Application of Molecular Imprinting Polymer Based Zero Current Potential Sensor for Benzidine / 分析化学

The effects of polymerization conditions including scan potential range, scan cycles, the concentration ratio of template molecules to functional monomer, pH of the buffer, and washing time for removing the template molecule from the imprinted polymer on the difference of zero current potential of benzidine ( BZ) interaction with BZ-MIP were investigated. The optimum preparations were obtained. The imprinted capacity of benzidine, 4-chloroaniline, and 4-aminobiphenyl and carmine was calculated as 0. 632, 0. 1123, 0. 1123, 0. 0847 and 0. 0725, respectively. This indicated that BZ-MIP had good specific recognition and selectivity to benzidine, and other substances did not interfere with the binding of BZ-MIP with BZ. The zero current potential variation was linear with the lorgarithm of BZ concentration in the range of 4í10-8-1í10-5 mol/Lwith detection limitation of 1. 89í10-8 mol/L. The sensor was used to detect BZ in waste water sample with recoveries of 95 . 7%-104 . 2%.

Research Progress of Molecular Imprinting Cryogel / 分析化学

Cryogel is a kind of elastic, spongy hydrogel prepared via addition polymerization from monomers or cross-linking reaction from a polymer at a temperature lower than the freezing point of the solvent. Cryogel has been principally used in molecular imprinting cryogel based solid phase extraction in the field of analytical chemistry, which combines both the advantages of high selectivity of the molecular imprinting and the porous structure, high throughput of a cryogel. Molecular imprinting cryogel can be used as the stationary phase in a packed column, a monolith column, or the adsorbent in a separation membrane. A variety of molecules can act as template molecules, including small molecules, macromolecules, a certain fragment of a macromolecule, and even an inorganic ion. Both a simple template and a complex template can be used. When employing more than a molecule ( or an ion) as templates simultaneously, the method is termed as Mixed template. While high abundance components of a complex sample act directly as mixed template, we name the method as Pending template. Further, while an analogue, an isotopic label, or a fragment of the target substance acts as a template, the method is defined as Dummy template. However, the research on cryogel is insufficient and the application of the cryogel is narrow hitherto.

Study on Preparation and Application of Surface Molecularly Imprinted Polymer Based on Mesopocous Molecular Sieve SBA-15 / 中国药房

OBJECTIVE:To prepare mesopocous molecular sieve SBA-15 surface molecularly imprinted polymer (SBA-15@MIP),and analyze the application of SBA-15@MIP in the determination of active micro-component. METHODS:Using baica-lein as the template molecule,acrylamide(AM)as the function monomer,tetrahydrofuran/ethanol(3∶2,V/V)as the polymeriza-tion solvent,ethylene glycol dimethacrylate(EGDMA)as the cross-linker,and 2,2-azobisisobutyronitrile(AIBN)as the initiator, SBA-15@MIP was synthesized on the surface of mesopocous molecular sieve SBA-15. The surface morphology and structure of the obtained polymer were characterized by TEM and FT-IR. Finally,the imprinted polymer was used as an adsorbent for solid-phase extraction (SPE) to detect baicalein in plasma samples by HPLC. RESULTS:It revealed that the well-ordered one-dimensional pore structure of SBA-15 was still preserved in the successful synthesized SBA-15@MIP,and baicalein molecule was imprinted suc-cessfully. The limit of detection(LOD)and limit of quantification(LOQ)for baicalein in plasma were 3.5 ng/ml and 11.6 ng/ml, respectively;the average recovery was 94.4%(RSD=2.9%). CONCLUSIONS:SBA-15@MIP is prepared successfully,and can be applied for the determination of active micro-component.