Preparation of pH-responsive Fe3O4/Poly (acrylic acid-stat-methyl methacrylate-block-(2-dimethylamino) ethyl methacrylate) magnetic composite microspheres and its application in controlled release of drug

Controlled radical polymerization based on 1, 1-diphenylethylene (DPE method) was used to prepare pH-responsive magnetic composite microspheres. By this method, Fe₃O₄/Poly (acrylic acid-stat-methyl methacrylate-block-(2-dimethylamino) ethyl methacrylate) (Fe₃O₄/P(AA-MMA-DMA)) microspheres were prepared via emulsifier free emulsion polymerization of acrylic acid (AA), methyl methacrylate (MMA) and (2-dimethylamino) ethyl methacrylate (DMA) using 1, 1-diphenylethylene (DPE) as radical control agent in the presence of Fe₃O₄ nanoparticles. The structure and properties of Fe₃O₄/P (AA-MMA-DMA) microspheres were characterized by IR, ¹H NMR, SEC-MALLS, TEM, TGA, VSM and DLS. The application of Fe₃O₄/P (AA-MMA-DMA) microspheres in controlled release of drug was also investigated. It was found that the DPE method allowed the preparation of pH-responsive magnetic composite microspheres, and Fe₃O₄/P (AA-MMA-DMA) microspheres obtained were pH-responsive, perfect sphere-shaped morphologies, superparamagnetism with a saturation magnetization of 14.36 emu/g, and high magnetic content with a value of 29%. Moreover, Fe₃O₄/P (AA-MMA-DMA) microspheres could control the release of phenolphthalein in a buffer solution by adjusting the pH value.     

Dispersion of luminescent nanoparticles in different derivatives of poly(ethyl methacrylate)

Gd2O3:Tb(5%) nanoparticles were prepared via the polyol route and dispersed without any stabilizer in several ethyl methacrylate derivatives matrices such as poly(ethyl methacrylate), poly(2-methoxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate) (PHEMA). Nanocomposites were obtained via free-radical polymerization of methacrylic monomers with ethylene glycol dimethacrylate as crosslinker and colloidal solution of Gd2O3:Tb(5%) nanoparticles. Best results are obtained with PHEMA in which the dispersed Gd2O3:Tb(5%) nanoparticles are spherical with a mean diameter of 15 nm, as measured by TEM. The obtained solid Gd2O3:Tb(5%)/PHEMA nanocomposites are highly transparent (in the visible spectral range) and exhibit characteristic photoluminescence of Tb3+ 5D4-7F(J) (J = 6-3), with 5D4-7F5 strong green emission at 536 nm upon UV excitation. The nanoparticles and nanocomposites have been well characterized by high-resolution transmission electron microscope (TEM), UV/Vis transmission spectra, photoluminescence excitation, and emission spectra.     

Preparation,properties, and drug release of thermo- and pH-sensitive poly((2-dimethylamino)ethyl methacrylate)/poly(<Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-diethylacrylamide) semi-IPN hydrogels

In this paper, a series of semi-interpenetrating polymer network (semi-IPN) hydrogels based on poly((2-dimethylamino)ethyl methacrylate)/poly (N,N-diethylacrylamide) (PDMAEMA/PDEA) were synthesized by changing the initial PDMAEMA/DEA molar ratio at room temperature. The influence of this additive on the property of resulting PDEA hydrogels was investigated and characterized. The interior morphology by scanning electron microscopy (SEM) revealed that the semi-IPN hydrogels have interconnected porous network structures. The glass transition temperature (T _g) of the semi-IPN hydrogels was observed by differential scanning calorimetry (DSC). Equilibrium swelling ratio (ESR), swelling and deswelling dynamics of the hydrogels responding to temperature and pH were investigated in detail. Compared to PDEA, the semi-IPN hydrogels exhibited excellent mutative values in response to an alternation of the temperature and pH, and showed fast swelling and deswelling rates in response to temperature and pH change. The release behaviors of the model drug, aminophylline, were found dependent on hydrogel compositions and environmental temperature. These results suggest that the stimuli semi-IPN hydrogel have potential application as intelligent drug carriers.     

单分散聚甲基丙烯酸乙酯的制备与性能研究

活性阴离子聚合为聚合物分子设计和合成提供了一种有效方法.以1,1二苯基己基锂(DPHLi)为引发剂,添加LiClO4络合剂,采用活性阴离子聚合体系制备了单分散聚甲基丙烯酸乙酯(PEMA).考察了聚合温度、引发剂、添加剂等工艺参数对聚合反应的影响规律,并研究了不同pH值聚甲基丙烯酸乙酯的降解性能.     

Novel glycerol crosslinked poly(methyl methacrylate) synthesized by chemo-enzymatic method for controlled release application

Novel glycerol crosslinked poly(methyl methacrylate)(PMMA) was synthesized in one step in the presence of cocktail of chemical initiator and the biocatalyst Novozym 435 under mild reaction conditions. The objective of the study was to investigate the feasibility of glycerol to crosslink PMMA by biocatalytic route and to explore glycerol crosslinked PMMA as controlled release vehicle Effect of reaction time, temperature, glycerol to methylmethacrylate ratio, and methacrylate to toluene ratio was studied. Glycerol crosslinked PMMA swelled 289(± 9)% in acetone and collapsed when immersed in water and in hexane. Swelling and shrinking of glycerol crosslinked PMMA was reversible in nature. Nanoparticles of glycerol crosslinked poly(methyl methacrylate) were synthesized by nanoprecipitation technique. The particles were spherical and of nanosize. The nanoparticles were used for the encapsulation and release of mosquito repellent N,N-diethyl-m-toluamide. Nanoparticles could encapsulate 8.5 mg of repellant in 4 h. The repellant got released from the nanoparticles at a controlled rate for a prolonged time interval. Release was more pronounced in deionized water and pH 7 buffer than in acetone. Addition of 1% NaCl further improved the release profile. 80% of encapsulated repellant was released from the nanoparticles in pH 7 buffer with 1% NaCl.     

Textural and tensile properties of thermo-responsive poly(2-(2-methoxyethoxy)ethyl methacrylate) hydrogel

Hydrogel dressings should be adhesive and elastic, while providing excellent functional and aesthetic features. Owing to weak intermolecular forces, various measures are undertaken to improve the hydrogel mechanical properties. Thermo-responsive poly(2-(2-methoxyethoxy)ethyl methacrylate) (poly(MEO₂MA)) hydrogel fabricated with different amounts of di(ethylene glycol) dimethacrylate (DEGDMA) cross-linker was characterised using texture profile analysis. More cross-linking sites incorporated within the hydrogel limit the swelling ability where 1.0 and 10?mol-% of DEGDMA swell by 8.03 and 1.92 times, at 5°C. Hydrogel textural and tensile property correlated with the cross-linker amount. Meanwhile, network structure disentanglement within swollen hydrogel reduced the force required for deformation. Thus, the swelling behaviour, textural and tensile properties were investigated to discern the possible biomedical applications suitable for this hydrogel.     

PMMA基凝胶聚合物电解质研究进展

综述了聚甲基丙烯酸甲酯(PMMA)基凝胶聚合物电解质(GPE)的研究进展,提出了PMMA基凝胶电解质目前主要存在的问题,着重讨论了采用共聚共混、交联和添加无机填料等对PMMA进行改性的方法,以及PMMA基GPE的三种制备方法.     

Synthesis and characterization of photocatalytic polyurethane and poly(methyl methacrylate) microcapsules for the controlled release of methotrexate

Abstract

The aim of this work is to prepare ultraviolet (UV) triggered controlled release of compounds from microcapsule systems (MCs). Polyurethane (PU) and poly(methyl methacrylate) (PMMA) microcapsules were studied with/without chemical functionalization using photocatalytic TiO₂ nanoparticles (NPs) on their surface. Once TiO₂ nanoparticles are illuminated with UV light (λ?=?370?nm), they initiate the rupture of the polymeric bonds of the microcapsule and subsequently initiate the encapsulated compound release, methotrexate (MTX) or rhodamine (Rh), in the present work. The size, polydispersity, charge, and yield of all MCs were measured, being the methotrexate drug release for all systems determined and compared with and without functionalization with TiO₂ NPs, under dark, visible light and UV illumination in vitro. Finally, the Rh release was characterized using fluorescence microscopy. The TiO₂ NPs size is around 10?nm, as determined by X-ray diffraction experiments. The PU MCs average size is around 60?µm, its electric charge +3.11?mV and yield around 85%. As for the PMMA MCs, the average size is around 280?µm, its electric charge ?7.2?mV and yield around 25% and 30% for both MTX and Rh, respectively. In general, adding TiO₂ NPs or the encapsulated products to the MCs does not affect the size but functionalization with TiO₂ NPs lowers the electric charge. Microcapsules functionalized with TiO₂ nanoparticles and irradiated with UV light presented the highest release of MTX and Rh. All other samples showed lower drug release levels when studied under the same conditions.     

Polyethyleneimine modified biocompatible poly(N-isopropylacrylamide)-based nanogels for drug delivery

A series of biocompatible and stimuli-sensitive poly(N-isopropylacrylamide-co-propyl acrylic acid) (P(NIPAAm-co-PAAc)) nanogels were synthesized by emulsion polymerization. In addition, polyethyleneimine (PEI) was further grafted to modify the PNIPAAm-based nanogels. The P(NIPAAm-co-PAAc)-g-PEI nanogels exhibited good thermosensitivity as well as pH sensitivity. Transmission electron microscopy (TEM) showed that the P(NIPAAm-co-PAAc)-g-PEI and P(NIPAAm-co-PAAc) nanogels displayed well dispersed spherical morphology. The mean sizes of the nanogels measured by dynamic light scattering (DLS) were from 100 nm to 500 nm at different temperatures. The cytotoxicity study indicated P(NIPAAm-co-PAAc) nanogels exhibited a better biocompatibility than both PNIPAAm nanogel and P(NIPAAm-co-PAAc)-g-PEI nanogel although all the three kinds of nanogels did not exhibit apparent cytotoxicity. The drug-loaded nanogels, especially the PEI-grafted nanogels, showed temperature-trigged controlled release behaviors, indicating the potential applications as an intelligent drug delivery system.     

Initiated chemical vapor deposition of pH responsive poly(2-diisopropylamino)ethyl methacrylate thin films

Poly(2-(diisopropylamino)ethyl methacrylate) (PDPAEMA) thin films were deposited on low temperature substrates by initiated chemical vapor deposition (iCVD) method using tertbutyl peroxide as an initiator. Very high deposition rates up to 38 nm/min were observed at low filament temperatures due to the use of the initiator. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy show the formation of PDPAEMA films with high retention of tertiary amine functionality which is responsible for pH induced changes in the wetting behavior of the surfaces. As-deposited PDPAEMA thin films on flat Si surface showed a reversible switching of water contact angle values between 87° and 28°; after successive treatments of high and low pH water solutions, respectively. Conformal and non-damaging nature of iCVD allowed to functionalize fragile and rough electrospun poly(methyl methacrylate) fiber mat surfaces by PDPAEMA, which creates a surface with a switching behavior between superhydrophobic and approaching superhydrophilic with contact angle values of 155 ± 3°and 22 ± 5°, respectively.     

Structure characterization of Ag-Ga/poly(methyl methacrylate) nanoparticles

The Ag-Ga/poly(methyl methacrylate) nanoparticles were prepared in-situ by emulsion polymerization method under ultrasonic irradiation without any initiators or metal reductant. HRTEM, EDS and XRD experiments were performed to characterize the nanoparticles. The results indicated that the nanocomposite particles possessed core-shell structure with diameters of 80-200 nm, as well as excellent monodispersity. The phenomenon that the polymer forms the shell via layer-by-layer self-assembly was found. XRD proved the existence of Ag0.72Ga0.28 and the probability of new Ag-Ga alloy because of two unknown diffraction peaks.     

Mesoporous silica nanoparticle-functionalized poly(methyl methacrylate)-based bone cement for effective antibiotics delivery

Poly(methyl methacrylate)-based bone cements are functionalized with mesoporous silica nanoparticles (MSN) to enable a highly efficient and sustained release of antibiotics to reduce the risk of post-operative joint infection. To overcome the limited drug release of 5% for only 1 day with the current commercial-grade bone cements, a 8 wt% MSN-formulated bone cement is able to increase the drug release efficiency by 14-fold and sustain the release for up to 80 days. The loaded MSN is suggested to build up an effective network of rod-shaped silica particles with uniformly arranged nanoporous channels, which is responsible for the effective drug diffusion and extend time-release to the external surfaces. MSN has no detrimental effect on the critical weight-bearing bending modulus and compression strength of bone cement. In vitro assay test results show a much sustained antibacterial effect and low cytotoxicity of MSN demonstrating the potential applicability of MSN-formulated bone cement.     

A thermosensitive chitosan-based hydrogel for controlled release of insulin

Present study aims at synthesizing a thermosensitive hydrogel for controlled release of insulin. According to a modified method, hydroxybutyl chitosan （HBC） hydrogel possessed thermal sensitivity is prepared which can form hydrogel at over 25℃. The HBC hydrogel is non-cytotoxic to mice fibroblasts cells （L929）. Insulin is 100% entrapped in the hydrogel, 38% of which is released in vitro from the concentration of 5% hydrogel after 48 h, whereas by enzymolysis with lysozyme, 80% of the total insulin is released after 48h. This study suggests that HBC hydrogel could be utilized for controlled release of insulin in a non-invasive manner.     

Synthesis and characterization of poly(N-vinylcaprolactam)-based spray-dried microparticles exhibiting temperature and pH-sensitive properties for controlled release of ketoprofen

Poly(N-vinylcaprolactam) (PNVCL) and poly(N-vinylcaprolactam-co-acrylic acid) (poly(NVCL-co-AA)) were synthesized by solution-free radical polymerization and displayed thermo-responsive behavior, with lower critical solution temperatures (LCSTs) of 35?°C and 39?°C, respectively. The incorporation of AA unities made the poly(NVCL-co-AA) sensitive to both pH and temperature. They were exploited in this work in preparing microparticles loaded with ketoprofen via spray-drying to modulate the drug release rate by changing pH or temperature. The interaction between polymer and drug was studied using X-ray diffractometry, Raman spectrometry and scanning electron microscopy (SEM). The biocompatibility of pure polymers, free ketoprofen as well as the spray-dried particles was demonstrated in vitro by low cytotoxicity and a lack of nitric oxide production in macrophages at concentrations as high as 100?µg/ml. The release profile of ketoprofen was evaluated by in vitro assays at different temperatures and pH values. Drug diffusion out of PNVCL’s hydrated polymer network is increased at temperatures below the LCST. However, when poly(NVCL-co-AA) was used as the matrix, the release of ketoprofen was primarily controlled by the pH of the medium. These results indicated that PNVCL and the novel poly(NVCL-co-AA) could be promising candidates for pH and temperature-responsive drug delivery systems.     

Reactive calcium-phosphate-containing poly(ester-co-ether) methacrylate bone adhesives: setting, degradation and drug release considerations

This study has investigated novel bone adhesives consisting of fluid photo-polymerizable poly(lactide-co-propylene glycol-co-lactide)dimethacrylate (PGLA-DMA) mixed with systematically varying fillers of β-tricalcium phosphate (β-TCP) and monocalcium phosphate monohydrate (MCPM), for the delivery of an antibacterial drug chlorhexidine (CHX). All formulations were found to polymerize fully within 200 s after exposure to blue light. In addition, water sorption by the polymerized materials catalyzed varying filler conversion to dicalcium phosphate (DCP) (i.e. brushite and monetite). With greater DCP levels, faster degradation was observed. Moreover, increase in total filler content enhanced CHX release, associated with higher antibacterial activity. These findings thus suggest that such rapid-setting and degradable adhesives with controllable drug delivery property could have potential clinical value as bone adhesives with antibacterial activity.     

聚甲基丙烯酸甲酯基网络稳定铁电液晶的制备及性能

通过热引发聚合制备了聚甲基丙烯酸甲酯基网络稳定铁电液晶(PNSFLC)材料。采用热台偏光显微镜观察了由不同含量的甲基丙烯酸甲酯(MMA)制备的PNSFLC样品的网络织构。采用紫外分光光度计在0～30V的电压条件下研究了PNSFLC样品的电光性能。采用阿贝折射仪在0～70℃范围内,研究了PSFLC的折射率随温度变化的关系。结果表明:随着(MMA)含量的增加,聚合物网络结构由稀疏至致密。当MMA含量为7%时,所制备的PNSFLC样品的电光响应比小分子液晶的电光性能成线性好,且该MMA含量的PNSFLC样品的热稳定性较好。     

Poly(2-hydroxyethyl methacrylate) wound dressing containing ciprofloxacin and its drug release studies

An improved wound dressing with a long-term drug diffusion-efficacy has been developed by UV-radiation technique. It involves incorporation of ciprofloxacin (CIP), at the concentration of 0.5–2.0% (w/v), into a water mixture of 2-hydroxymethacrylate (HEMA) monomer, benzoin isobutyl ether (BIE) initiator and different content of ethylene glycol dimethacrylate (EGDMA) cross-linker. Increasing the concentration of EGDMA would reduce the releasing ratio of CIP from pHEMA. T_1/2 is increased from 2.64 to 45.67 h when the EGDMA is added from 1 to 8%. In the ranges of , the n value of 1%CIP-pHEMA membranes is increased from 0.48 to 0.81. It indicates that the mechanism of drug release falls between the Fickian and Case II diffusion model. The antibacterial activity of the drug impregnated into the membrane was evaluated by in vitro drug kinetic agar plate method. Higher concentration of EGDMA, up to 8% of the cross-linker, extends the drug release. Comparison with the drug-soaked membranes, the newly synthesized 1% CIP-pHEMA membrane (cross-linked with 4% EGDMA) sustains the release of the entrapped drug and maintains the antibacterial activity up to 12 days.     

Evaluation of biocompatibility of the copolymer of 2-hydroxyethyl methacrylate with 2-(methylsulfanyl)ethyl methacrylate

This study compares subcutaneous and intracerebral biocompatibilty of two hydrogels: copolymer of 2-hydroxyethyl methacrylate with 2-(methylsulfanyl)ethyl methacrylate and poly(2-hydroxyethyl methacrylate) as reference polymer. The experimental copolymer was more biologically inert than poly(2-hydroxyethyl methacrylate) in both the studied parameters, hence the former material is a suitable candidate for biomedical application.     

Synthesis and characterization of hydrogels based on poly(2-hydroxyethyl methacrylate) for drug delivery under UV irradiation

The present study aims to create a controlled release system through the preparation and characterization of hydrogels based on 2-hydroxyl ethyl methacrylate (HEMA). In order to investigate the influence of photo-initiators on the drug release behavior of the resulting hydrogels, three different photo-initiators [2,2-dimethoxy-2-phenyl-acetophenone] (Irgacure 651), 1-hydroxycyclohexyl phenyl ketone (Irgacure 184) and 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959) were used. In addition, hydroxyapatite (HAp) was employed to modify HEMA hydrogels. The synthesis of hydrogels was confirmed by characterization through Fourier transform infrared spectroscopy, nuclear magnetic resonance (¹³C NMR) spectroscopy and digital microscope. The responsive behaviors were investigated by recording swelling ratios under different conditions. In vitro drug release studies were performed for donepezil hydrochloride-loaded hydrogels at pH 1.2, 6.8 and 7.4. The results indicated that hydrogels synthesized using Irgacure 2959 released the maximum amount of donepezil hydrochloride. Moreover, the release rate decreased in the presence of HAp.     

Thermal analysis of poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels

The influence of water on the physical properties of a hydrogel is important for understanding natural tissues and in designing synthetic materials to replace them. In this study, poly (2-hydroxyethyl methacrylate) (pHEMA) was used as a model system to understand how water interacts with the polymer of a hydrogel. Thermal analysis methods (thermogravimetric analysis coupled to mass spectrometry and differential scanning calorimetry) were used to determine: (i) the total water content of pHEMA gels; (ii) how this water was lost during heating; (iii) the relationship between water content of the gel and its glass transition temperature; and (iv) the behavior of the water in the gel on cooling. Previous researchers have invoked various models to describe the organization of water in a hydrogel. In this study, the simplest model which could explain all of the results from the different thermal analysis techniques was one which consisted of three classes of water: (i) hydration water in close proximity to the polymer; (ii) interstitial water in regions or cavities surrounded by polymer chains; and (iii) bulk water.