Halloysite Nanotube Composited Thermo-responsive Hydrogel System for Controlled-release

Halloysite nanotube-composited thermo-responsive hydrogel system has been successfully developed for controlled drug release by copolymerization of N-isopropylacrylamide (NIPAM) with silane-modified ha...     

甲基纤维素湿敏水凝胶中溶菌酶微球性质的体外评价

Long-terrn injectable microspheres have some inherent disadvantages such as migration of microspheres from the originalsite an.d the burst effect. In order to avoid these problems, microsphere-loaded thermosensitive, hydrogel system was designed and expected to achieve a zero-order release Of biomolecular drugs in relativehigh initial drug loadings. Lysozyme, an antibacterial protein usually used to reduce prosthetic valve endocarditis,was selected as the model drug. Poly （DL-lactide-co-glycolide） （PLGA） microspheres, prepared by solvent evaporation method, were employee to encapsulate lysozyme and dispersed into thermosensitive pre-gel solution containing methylcellulose （MC）, polyethylene glycol （PEG）, sodium citrate （SC）, and sodium alginate （SA）. The mixture could act asadrug reservoir by.performing sol-gel transition rapidly if the temperature was raised from roomtemperature to 37℃. The in vitro release results showed that the burst effect was avoided due to strengthening ofdiffusion resistance in the gel. The formulation was able.to deliver lysozy.me for over.30 daysin a nearly zero-order release profile with a rate of 32.8μg.d^-1 which exhibits its remarkable potential for effective aoolication in long-term drug delivery.     

Study on Synthesis and Chloramphenicol Release of Poly（2-hydroxyethylmethacrylate-co-acrylamide） Hydrogels

In this article, poly（2-hydroxyethylmethacrylate-co-acrylamide） hydrogels were synthesized by bulk free-radical copolymerization of 2-hydroxyethylmethacrylate （HEMA） and acrylamide （AAm） for soft contact lens（SCL）-based ophthalmic drug delivery system. The copolymer was characterized with FT-IR and SEM, the swelling property of the hydrogels were studied by gravimetrical method, and chloramphenicol was used as a model drug to investigate drug release profile of the hydrogels. The results showed that poly（2-hydroxyethylmethacrylateco-acrylamide） hydrogels were transparent and useful SCL biomaterial, the water content increased as AAm content increase and pH decrease, and in the same way, hydrogel composition affected chloramphenicol release process too. Migration rate of chloramphenicol increased as the AAm content in the hydrogels increased in the first stage of diffusion process, whereas there was no significant difference thereafter.     

扩散控制型混合药膜包膜体系缓释的数学模型

A release model for diffusion-controlled monolithic matrix coated with outer membrane system is proposed and solved by using the refined double integral method. The calculated results are in satisfactory agreement with the experimental release data. The present model can be well used to describe the release process for all Cd/Cs.values. In addition, the release effects of the monolithic matrix coated with outer membrane system are discussed theoretically.     

Thermosensitive Poly(N-isopropylacrylamide-co-acrylonitrile) Hydrogels with Rapid Response

Acrylonitrile （AN） was copolymerized with N-isopropylacrylamide （NIPA） to synthesize thermosensitive hydrogels, and the on-off switch behavior of poly（NIPA-co-AN） hydrogels with different fraction of hydrophobic component （AN） was investigated. It is found that the lower critical solution temperature （LCST）, the swelling ratio at certain temperature and the reswelling rate of poly（NIPA-co-AN） hydrogels decreased as AN unit fraction in copolymers increased. In order to improve the responsive rate of poly（NIPA-co-AN） hydrogels, they were further treated by surface crosslinking using N, N′-methylene bisacrylamide （BIS） as a crosslinking agent. The swelling and deswelling behaviors of these copolymers were compared with those of the untreated hydrogels. The results indicated that the responsive rate of poly（NIPA-co-AN） hydrogel was improved by surface crosslinking. The resulting hydrogels bearing cyano groups with fast response have potential applications in the field of drug-controlled release and immobilization of biomolecules.     

富镧稀土镍-苯浆液体系中液相苯加氢反应动力学研究

The kinetics of liquid-phase hydrogenation of benzene in misch metal nickel-five (MlNi5) and benzene slurry system was studied by investigating the influences of the reaction temperature, pressure, alloy concentration and stirring speed on the mass transfer-reaction processes inside the slurry. The results show that the whole process is controlled by the reaction at the surface of the catalyst. The mass transfer resistance at gas-liquid interface and that from the bulk liquid phase to the surface of the catalyst particles are negligible. The apparent reaction rate is zero order for benzene concentration and first order for hydrogen concentration in the liquid phase. The kinetic model obtained fits the experimental data very well. The apparent activation energy of the hydrogen absorption reaction of MlNi5-C6H6 slurry system is 42.16 kJ.mol-1.     

An investigation on dissolution kinetics of single sodium carbonate particle with image analysis method

Dissolution kinetics of sodium carbonate is investigated with the image analysis method at the approach of single particle. The dissolution experiments are carried out in an aqueous solution under a series of controlled temper-ature and pH. The selected sodium carbonate particles are al spherical with the same mass and diameter. The dissolution process is quantified with the measurement of particle diameter from dissolution images. The concentration of dissolved sodium carbonate in solvent is calculated with the measured diameter of particle. Both surface reaction model and mass transport model are implemented to determine the dissolution mecha-nism and quantify the dissolution rate constant at each experimental condition. According to the fitting results with both two models, it is clarified that the dissolution process at the increasing temperature is controlled by the mass transport of dissolved sodium carbonate travelling from particle surface into solvent. The dissolution process at the increasing pH is control ed by the chemical reaction on particle surface. Furthermore, the dissolution rate constant for each single spherical sodium carbonate particle is quantified and the results show that the disso-lution rate constant of single spherical sodium carbonate increases significantly with the rising of temperature, but decreases with the increasing of pH conversely.     

醋酸脱水过程中对二甲苯+(醋酸,醋酸甲酯,醋酸正丙酯)和醋酸甲酯+醋酸正丙酯的二元汽液相平衡(英文)

The vapor-liquid equilibrium data of four binary systems (acetic acid +p-xylene, methyl acetate +n-propyl acetate, n-propyl acetate +p-xylene and methyl acetate +p-xylene) are measured at 101.33 kPa with Ellis equilibrium still, and then both the NRTL and UNIQUAC models are used in combination with the HOC model for correlating and estimating the vapor-liquid equilibrium of these four binary systems. The estimated binary VLE results using correlated parameters agree well with the measured data except the methyl acetate +p-xylene system which easily causes bumping and liquid rushing out of the sampling tap due to their dramatically different boiling points. The correlation results by NRTL and UNIQUAC models have little difference on the average absolute deviations of temperature and composition of vapor phase, and the results by NRTL model are slightly better than those by UNIQUAC model except for the methyl acetate +n-propyl acetate system, for which the latter gives more accurate correlations.     

载三氧化二砷的PEG—PLGA隐性纳米粒的制备及体外研究

The aim of this study was to prepare arsenic trioxide （ATO）-loaded stealth PEGylated PLGA nanoparticles （PEG-PLGA-NPs） and to assess the merits of PEG-PLGA-NPs as drug carriers for ATO delivery. PEG-PLGA copolymer was synthesized with methoxypolyethyleneglycol （Mw=5000）, D, L-lactide, and glycolide by the ring-opening polymerization method. Amorphous ATO was transformed into cubic crystal form to increase its solu-bility in the organic solvent. ATO-loaded PEG-PLGA-NPs were prepared by the modified spontaneous emulsification solvent diffusion （SESD） method, and the main experimental factors influencing the characteristics of nanopar- ticles were investigated, to optimize the preparation. To confirm the escape of PEG-PLGA-NPs from phagocytosis by phagocytes, PEG-PLGA-NPs labeled rhodamine B uptake by murine peritoneal macrophages （MPM） were analyzed by flow cytometry. The results showed that the physicochemical characteristics of PEG-PLGA-NPs were affected by the type and concentration of the emulsifiers, polymer concentration, and drug concentration. ATO-loaded PEG-PLGA-NPs, with particle size of 120.8nm, zeta potential of-10.73mV, encapsulation efficiency of 73.6%, and drug loading of 1.36%, were prepared under optimal conditions. The images of transmission electron micros-copy （TEM） indicated that the optimized nanoparticles were near spherical and without aggregation or adhesion. The release experiments in vitro showed the ATO release from PEG-PLGA-NPs exhibited consequently sustained release for more than 26d, which was in accordance with Higuchi equation. The uptake of PEG-PLGA-NPs by MPM was found to decrease markedly compared to PLGA-NPs. The experimental results showed that PEG-PLGA-NPs were potential nano drug delivery carriers for ATO.     

Removal of diclofenac from aqueous solution with multi-walled carbon nanotubes modified by nitric acid☆

Modified multi-walled carbon nanotubes (MWCNTs) were used as adsorbents for removal of diclofenac. The re-action conditions were examined. Langmuir, Freundlich, Temkin, and Dubinin–Radushkevich isotherm models were applied to determine appropriate equilibrium expression. The results show that the experimental data fit the Freundlich equation well. Thermodynamic parameters show that the adsorption process is spontaneous and exothermic. The kinetic study indicates that the adsorption of diclofenac can be well described with the pseudo-second-order kinetic model and the process is controlled by multiple steps.     

温敏聚N-异丙基丙烯酰胺的载药和释药性能研究

以对乙酰氨基酚为模型药物分子,温敏水凝胶聚N-异丙基丙烯酰胺(PNIPAAm)为载体,研究了药物在凝胶上的负载和在不同温度(25和37℃)下磷酸盐缓冲溶液(pH 7.4)中的释放行为.结果表明,对乙酰氨基酚的负载量约为35wt％,并且与载体PNIPAAm存在氢键作用.药物在磷酸盐缓冲溶液中的体外模拟释放结果显示,当温度(37℃)高于凝胶的LCST时,对乙酰氨基酚释放的较慢;当温度(25℃)低于其LCST时,释放的较快.因此,可通过环境温度的改变达到APAP在载体PNIPAAm上控制释放的目的.     

Synthesis and Properties of Temperature-Sensitive Hydrogel Based on Hydroxyethyl Cellulose

Hydrogels were prepared from modified hydroxyethyl cellulose by copolymerization with N-isopropylacrylamide. The equilibrium swelling ratio of hydrogel was measured in buffer solution with pH 7.0 from 25.0 to 45.0°C and the data obtained showed that hydrogels exhibited temperature sensitivity. The results of DSC analysis revealed that the low critical solution temperature (LCST) of hydrogels was enhanced by the introduction of hydroxyethyl cellulose. SEM images suggested that the cross-section of freeze-dried hydrogels was porous. The data of adsorption and release experiments for two model drugs suggest that the controlled drug release can be achieved.     

A Composite Thermo‐Responsive Membrane System for Improved Controlled‐Release

A novel composite thermo‐responsive membrane system for improved controlled‐release is successfully developed. The membrane is composed of a porous membrane with grafted poly(N‐isopropylacrylamide) (PNIPAM) gates acting as functional valves, and a cross‐linked PNIPAM hydrogel inside the reservoir acting as the solute carrier. The thermo‐responsive controlled‐release characteristics of the proposed system are studied when the ambient temperature is continuously increased from 20 to 45 °C (across the LCST of PNIPAM) at a constant rate of 1.5 °C/min. The experimental results show that the prepared system exhibits significantly better performance for thermo‐responsive controlled‐release than single‐functional systems currently in existence, due to the cooperative action of the gating membrane and the inner cross‐linked hydrogel. Furthermore, due to the distinctive composite architecture, the proposed system can overcome some inherent disadvantages of current systems, such as the drug security problem of the reservoir‐type systems and the mechanical strength problem of the hydrogel matrix‐type systems. The system proposed in this study provides a new mode for thermo‐responsive controlled‐release.     

Design of microcapsules with hydrogel as a membrane component and their preparation by a spouted bed

This paper describes particulate design and preparation to control drug release thermosensitively or in a delayed mode from microcapsules (MCs) that were prepared by coating with a membrane incorporating hydrogel as a particulate or chemical component. The particulate preparation was carried out by a spouted bed coating process. The microcapsules releasing drug with a positive thermosensitivity were prepared by dispersing the newly developed latex particles in the ethylcellulose matrix membrane. The latex particles were synthesized so as to have a thermoinsensitive core and a thermosensitive poly(N-isopropylacrylamide) hydrogel shell. Poly(N-isopropylacrylamide) with a lower critical solution temperature (LCST) at 32 °C in water shrank at higher temperatures and highly swelled at lower temperatures than LCST, leading to so-called positively thermosensitive release. On the other hand, when the acrylic ter-polymer of latex particles has a hydrophilic component, 2-hydroxyethyl methacrylate, the water uptake rate of microcapsules could be controlled by its content in the ter-polymer and membrane thickness. The release was characterized by a delayed mode; then the lag time was controlled by the 2-hydroxyethyl methacrylate content and the membrane thickness. This content was also related to the mechanical flexibility of membrane that was critical in the release rate control after the release of drug starts.     

Radiation polymerization and controlled drug release of polymer hydrogels with NIPA and NVP

P(NIPA–NVP) and P(NIPA)/PVP interpenetrating polymer network hydrogels were synthesized by radiation polymerization in this article. Acetylsalicylic acid proved a model drug of salt resistance. Drug‐controlled release of these hydrogels containing acetylsalicylic acid was investigated. Influences of radiation dose, feed composition on the lower critical solution temperature (LCST), swelling behavior, salt dissolubility, and controlled release effect were discussed. The preferable preparation conditions for the titled aim were dose rate of 1 KGy/h, total dose of 30 KGy, feed monomer ratio of NIPA:NVP between 1:1 and 4:1, and total monomer concentration of 10%. As NVP content of the hydrogel increased, LCST rose, swelling ratios increased, salt resistance improved, and both swelling and deswelling rates slowed. Due to the ability of forming association complex, these hydrogels had the function of solubilization that made the drug release of difficult dissoluble medicine effective. These hydrogels had a higher drug release at physiological environment. The experimental results showed that these hydrogels were promising materials for causing solubilization and developing a long‐term controlled release system. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 724–729, 2003     

Synthesis and characterisation of thermo-sensitive terpolymer hydrogels for drug delivery applications

In this study, thermo-sensitive terpolymer hydrogels based on N-tert-butylacrylamide (NtBAAm), N-isopropylacrylamide (NIPAAm) and N-vinyl pyrrolidone (NVP) were successfully photopolymerised and characterised. 1-hydroxy-cyclohexylphenylketone (Irgacure 184) and 2-hydroxy-2-methyl-1-phenyl-propanone (Irgacure 2959) were used as light-sensitive initiators to initiate the reactions. Chemical structures of the hydrogels were confirmed using Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. The hydrogels were also characterised using modulated differential scanning calorimetry (MDSC) for their glass transition and phase transition temperatures. A single glass transition temperature (T _g ) was observed, further confirming successful formation of a terpolymer. The hydrogels were thermo-responsive, exhibiting a decrease in lower critical solution temperature (LCST) as the NtBAAm weight ratio was increased. Pulsatile swelling studies indicated that the hydrogels had thermo-reversible properties and the swelling properties were dependent on test temperature, monomer feed ratios and crosslinker content. The proposed hydrogel system could find applications in a broader field of gel/drug interaction, for the development of controlled release and targeted delivery devices.     

Preparation and characterization of thermo‐sensitive poly(vinyl alcohol)‐based hydrogel as drug carrier

Poly(vinyl alcohol)s (PVA) with high and low molecular weights were chemically modified by introducing acetaldehyde onto the polymer backbone to induce thermal‐responsive properties. The influence of both molecular weight ( ) and acetalization degree on the lower critical solution temperature (LCST) of thermo‐sensitive polymer was investigated. Moreover, a temperature responsive hydrogel was prepared by controlled cross‐linking of acetalized poly(vinyl alcohol) (APVA) and glutaraldehyde. As a model drug, ciprofloxacin was introduced into the prepared thermal sensitive hydrogel to reveal the drug loading and release behaviors. The structure, thermo‐sensitivity, swelling/deswelling kinetics, morphology, and drug loading/release behaviors were also investigated. The results indicated that the APVA polymer solution exhibited temperature responsivity, and APVA with high acetalization degree showed low LCST, whereas those with high PVAs showed high LCST. Meanwhile, morphology study was identical with the swelling/de‐swelling behavior. The loading and release of ciprofloxacin were controllable. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39720.     

Synthesis of biodegradable thermo- and pH-responsive hydrogels for controlled drug release

Novel intelligent hydrogels composed of biodegradable and pH-sensitive poly(l-glutamic acid) (PGA) and temperature sensitive poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) (PNH) were synthesized and characterized for controlled release of hydrophilic drug. The influence of pH on the equilibrium swelling ratios of the hydrogels was investigated. A higher PNH content resulted in lower equilibrium swelling ratios. Although temperature had little influence on the swelling behaviors of the hydrogels, the changes of optical transmittance of hydrogels as a function of temperature were marked, which showed that the PNH part of hydrogel exhibited hydrophobic property at temperature above the lower critical solution temperature (LCST). The biodegradation rate of the stimuli-sensitive hydrogels in the presence of enzyme was directly proportional to the PGA content. Lysozyme was chosen as a model drug and loaded into the hydrogels. The in vitro drug release experiment was carried out at different pH values and the release data suggested that both the pH and PNH content played important roles in the drug release behaviors of the hydrogels.     

APPARENT NON-FICKIAN RELEASE FROM A SCLEROGLUCAN GEL MATRIX

Hydrogels, and particularly biopolymeric hydrogels, have recently received tremendous interest as controlled release systems for their peculiar features such as high biocompatibility, biodegradability, bioadhesivity, chemical and thermal resistance and good mechanical properties. Among biopolymers, the exocellular microbial polysaccharide scleroglucan appears to be particularly well suited for the formulation of monolithic hydrogel matrices for controlled drug release. In this work we studied the macroscopic factors influencing the kinetics of a model drug release (theophylline) from a scleroglucan hydrogel matrix (2%w/w) and modeled the relevant experimental results. The evidences for the release experiments indicate that the kinetics of the processes follow an apparently non-Fickian behavior under different active drug concentration, temperature and stirring speed. However, by considering the peculiar nature of the hydrogel matrix and the geometrical features of the experimental setup in the formulation of the appropriate initial and boundary conditions, data can be satisfactorily modeled with the classical Fick's law.