载5-氟尿嘧啶壳聚糖/明胶微粒的制备及药物释放性能

壳聚糖及明胶是生物相容性良好的高分子药物载体,制备载5-氟尿嘧啶壳聚糖/明胶微粒,并进行体外释药研究。以石蜡油为外相,壳聚糖/明胶为内相,用乳化交联法制备微粒,以吸附药量为指标,采用正交设计实验优化获得最佳制备条件,用红外光谱、SEM对最佳条件下制备的微粒进行表征。结果表明壳聚糖/明胶微粒的最佳制备条件如下:水油比1:7,壳聚糖/明胶浓度比1:3,乳化剂100.7mmol/L,乳化5min,乳化温度60℃,交联剂戊二醛用量5.5mmol/L,交联时间1h。在此条件下,载药微粒的载药量为34.93%,包封率为38.36%。红外光谱图表明壳聚糖/明胶微粒已负载5-氟尿嘧啶,SEM表明微粒成球状,表面较光滑。模拟胃肠释放表明,微粒具有一定的缓释性能。采用乳化交联法制备载5-氟尿嘧啶壳聚糖/明胶微粒方法简单,重现性好,且其体外释放实验显示出明显的缓释作用。     

药物控释用智能水凝胶研究进展

智能水凝胶在药物控释方面具有智能化、效率高和安全方便等优点.近年来,研究开发药物控释用智能水凝胶非常活跃,展示了广阔的应用前景.本文综述了药物控释用温度、pH值、葡萄糖、电场、磁场及光敏感水凝胶的最新研究进展.     

Development of polyampholyte hydrogels based on laponite for electrically stimulated drug release

Polyampholyte hydrogels (PAHs) composed of laponite, polyacrylamide and poly(3‐acrylamidopropyl)trimethylammonium chloride crosslinked with ethylene glycol dimethacrylate were synthesized and characterized for their sensitivity to external conditions and their ability to control the release of the active drug agent paracetamol. Three PAHs were synthesized by taking the weight ratio of laponite to total monomer as 7, 15 and 29%. PAHs were characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis and swelling measurements carried out in various media. Equilibrium and pulsatile swelling studies were performed on all hydrogels to determine to what extent the hydrogels would respond to changes in environmental pH, ionic strength and electric field, and how fast that response would be. Paracetamol was loaded into the hydrogels, and was released into buffered solutions as a function of pulsatile changes in pH and electric field. © 2014 Society of Chemical Industry     

Evaluation of the influence of spirulina microalgae on the drug delivery characteristics of genipin cross-linked chitosan hydrogels

Abstract

Chitosan-spirulina hydrogels were prepared by crosslinking of chitosan with genipin, in presence of spirulina microalgae. The swelling ratios and kinetic parameters of the hydrogels in distilled water, pH:2 and pH:7.4 solutions and the drug 5-Fluorouracil delivery capacities of the hydrogels were determined by gravimetric and spectrophotometric analyses, respectively and the results were statistically evaluated. The morphological structures, thermal and mechanical properties of the hydrogels were investigated using related techniques. Furthermore, cytotoxicity test was performed for assessment of biocompability of the hydrogels.The all results indicate that spirulina significantly improves the drug delivery properties of the genipine cross-linked hydrogels.     

Poly(HEMA-co-AAm)水凝胶对氯霉素的缓释作用

采用本体共聚法制备poly(HEMA-co-AAm)（甲基丙烯酸羟乙酯与丙烯酰胺共聚物）水凝胶,采用恒温释放方法研究了poly(HEMA-co-AAm)水凝胶对氯霉素的缓释作用。结果表明,随水凝胶中AAm组分的含量增大,水凝胶对氯霉素的吸收量增大,氯霉素的释放速率也相应增大;随缓释介质的pH值下降,氯霉素的释放速率增大;在初始释放阶段,氯霉素的迁移速率随水凝胶中AAm组分的含量增大而增大,但随后并无明显影响。     

导电水凝胶的制备及应用研究进展

导电水凝胶是一类将亲水性基质和导电介质有机结合的新型水凝胶,具有较高的柔韧性、可调的力学性能和优异的电化学性能,在柔性电子设备等领域具有广阔的应用前景。本文综述了导电水凝胶材料的研究前沿和动态,介绍了导电水凝胶的分类及制备方法,讨论了导电水凝胶的结构设计与性能,重点阐述了导电水凝胶材料的应用研究进展,归纳了导电水凝胶材料面临的问题与挑战,并展望了导电水凝胶材料的发展趋势,指出采用天然可再生资源为原料开发具有高导电性、力学性能稳定、耐极端温度、生物相容性和生物可降解的导电水凝胶将成为下一步研究重点,同时优化柔性电子装置、提高器件输出稳定性也将成为重要的研究方向之一。导电水凝胶的制备及应用研究将促进柔性电子功能材料领域的快速发展。     

Effect of graphene oxide on the pH-responsive drug release from supramolecular hydrogels

Polypseudorotaxane (PPR) hydrogels formed by inclusion complexes between poly(ethylene glycol) (PEG) and α-cyclodextrin (α-CD) are highlighted as promising biomaterial for drug delivery. Here, we report a novel injectable PPR hydrogel containing graphene oxide (GO) for pH-responsive controlled release of doxorubicin hydrochloride (DOX). Our results showed that the gelation rates of the PEG/α-CD supramolecular structures could be tailored depending on the reagent concentrations. The formation of PEG/α-CD inclusion complexes was confirmed by TEM and XRD, the latter further confirming that GO restricts their formation. The supramolecular hydrogels were easily loaded with DOX by simple addition into the PEG solution before the complex formation with the α-CD solution. Noteworthy, disruption of ionic interactions between DOX and GO in the nanocomposite at pH = 5.5 resulted in higher DOX release than under physiological conditions (pH = 7.4). This pH dependence was barely observed in pure PPR hydrogel. These findings introduce DOX-loaded supramolecular hydrogels nanocomposites as promising carriers for pH-responsive and therefore localized, drug delivery systems.     

In vitro release kinetics of bovine serum albumin from highly swellable dextran hydrogels

Hydrogels synthesized from a polysaccharide‐based polymer, dextran, in the presence of two crosslinking agents, N,N′‐methylenebisacrylamide and epichlorohydrin, were evaluated for the oral colon‐specific delivery of polypeptide drugs. These novel dextran hydrogels had significantly greater swelling ratios than recently developed dextran hydrogels. A model protein, bovine serum albumin, was loaded into 50% (by weight) crosslinker‐containing dextran hydrogels in two ways: during the crosslinking reaction and by a soaking method. The loading capacity was varied between 22 and 25 mg/g of dry gel, depending on the loading procedure. In vitro release experiments were performed with a simulated gastrointestinal system in the presence and absence of dextranase. The diffusion exponents were calculated by means of a semiempirical power‐law equation for the release of protein from swellable hydrogel discs. Bovine serum albumin was mainly released by Fickian diffusion, and this indicated that its hydrodynamic diameter (7.7 nm) was smaller than the hydrogel mesh size (～19 nm). The release of bovine serum albumin from both hydrogel types was substantially higher than expected, especially in the presence of dextranase, and this was attributed to the high swellability of the hydrogels. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Magnetic field responsive methylcellulose-polycaprolactone nanocomposite gels for targeted and controlled release of 5-fluorouracil

5-Fluorouracil loaded magnetic field sensitive methylcellulose and polycaprolactone gels were prepared and characterized by FTIR, XRD, TGA, SEM, and VSM. Swelling analysis supplied important information on drug diffusion properties. The release profile of gels was investigated in different buffer solutions and the highest release values were observed at pH = 7.2. Release kinetic was analyzed using an empirical equation to clarify the transport properties of drug. The effects of nanoparticle concentration and applying external magnetic field were investigated on release profile. The results indicated that the drug release decreased by both, applying external magnetic field and increasing the concentration of Fe₃O₄ nanoparticles.     

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     

Effect of sodium hexametaphosphate concentration on the swelling and controlled drug release properties of chitosan hydrogels

An ionically crosslinked polymer network composed of chitosan and sodium hexametaphosphate (SHMP) was synthesized to determine their swelling and ascorbic acid release kinetics at various SHMP concentrations. The chitosan/SHMP hydrogels were synthesized using an acetic acid aqueous solution (1% v/v). Ionization constants (pK_b) of the SHMP were obtained by potentiometric titration. The results show that the SHMP was hydrolyzed in acidic medium forming orthophosphate and trimetaphosphate. The swelling percentages were measured at different swelling media pH's; the higher swelling capacities were for the systems that were swollen in neutral solution. Also, it was studied the ionic crosslinking degree by turbidimetric titration, comparing the electrostatic interactions between the chitosan and the SHMP; the results shows that electrostatic interactions between the amine groups of the chitosan and the anionic groups of the SHMP are dependent of the swelling medium pH. The ascorbic acid diffusion inside the hydrogel follows the second law of Fick, and the diffusion coefficients were obtained for different SHMP concentrations. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

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.     

Rheological properties and drug release characteristics of pH‐responsive hydrogels

Rheological properties, blend compatibility, and gel‐forming capacity of carbopol 940 (CP‐940), sodium alginate (NaAlg), and guar gum (GG) have been studied. These matrices have been used in delivery of timolol maleate for ophthalmic applications. Aqueous solutions of CP‐940, NaAlg, and GG in concentrations between 0.1 and 1% (wt/vol) and their blends have been prepared. In situ gel forming polymeric solutions have shown an increase in viscosity upon exposure to specific pH, ions, and temperature of the eyeball. Blend miscibility was studied by calculating polymer–polymer interaction parameters using viscosity data. Rheological properties viz., torque, viscosity, shear stress, and shear rate were obtained using a Brookfield rheometer. Viscosities of polymer solutions were obtained by a Schott Gerate viscometer. Rheological data were analyzed using Bingham, Casson Standard, and Casson Chocolate equations. The hydrogels were subjected to ex vivo release studies on timolol maleate through the excised bovine cornea using a modified Franz diffusion cell. Results were compared with the conventional drug solution. The release could be extended when the drug is incorporated into hydrogel‐forming solution. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2057–2064, 2004     

Application of minimally invasive injectable conductive hydrogels as stimulating scaffolds for myocardial tissue engineering

So far, several methods for myocardial tissue engineering have been developed to regenerate myocardium and even create contractile heart muscles. Among these approaches, hydrogel based methods have attracted much attention due to their ability to mimic the architecture of native extracellular matrix. Injectable hydrogels are a specific class of hydrogels which can be formed in situ by physical and/or chemical crosslinking. Generally, using these hydrogels is more advantageous because they are minimally (less) invasive in comparison with open surgery. Moreover, with respect to the fact that ‘myocardium is a conductive tissue’, utilization of conductive polymers for myocardial tissue engineering has demonstrated promising results. Both the injectable hydrogels and conductive polymers have some merits and demerits, but studies show that using a combination of them has prominently enhanced regeneration of the myocardium. In this review, the focus is on injectable hydrogels, conductive polymers and injectable conductive hydrogels for myocardial tissue engineering. © 2018 Society of Chemical Industry     

印迹水凝胶作为氟尿嘧啶载体的药物缓释性能

以氟尿嘧啶为模板药物,以甲基丙烯酸羟乙酯为骨架单体,以甲基丙烯酸为功能单体,乙二醇二甲基丙烯酸酯为交联剂,偶氮二异丁腈为引发剂合成印迹水凝胶,并通过扫描电镜、红外光谱及差示热量扫描等测试手段对凝胶进行了表征,结果表明：制备的印迹水凝胶表面无孔、光滑,氟尿嘧啶与其中的单体通过氢键结合成了复合物,同时经处理后凝胶中已不再残留未反应的单体。印迹水凝胶的吸水溶胀性能实验结果显示其吸水溶胀性能随制备中模板药物的含量的增加而增强,同时同一凝胶的溶胀速度与溶胀率随体系pH值的升高而增强。在氟尿嘧啶溶液中测定水凝胶的药物负载量,结果显示：印迹水凝胶的药物负载能力明显强于非印迹水凝胶,同时印迹水凝胶（8∶1）对药物的负载能力强于印迹水凝胶（4∶1）,药物负载量高达0.0914 mg/g。在模拟体液中测试水凝胶对药物的释放效果结果显示：印迹水凝胶对药物的缓释作用明显优于非印迹水凝胶,并且印迹水凝胶（8∶1）对药物的缓释效果优于印迹水凝胶（4∶1）,对药物的释放平缓,同时,释放体系pH值的升高不利于印迹水凝胶的药物缓释效果。     

Thermoreversible hydrogels. XV. Swelling behaviors and drug release for thermoreversible hydrogels containing silane monomers

Three series of thermosensitive copolymeric hydrogels were prepared from [3‐(methacryloyloxy)propyl]trimethoxysilane (MPTMOS), [2‐(methacryloyloxy)ethoxy]trimethylsilane (METMS), and (methacryloyloxy)trimethylsilane (MTMS), referred to as the silane monomer, and N‐isopropylacrylamide (NIPAAm) by solution polymerization. The influence of the structures and amounts of silane monomers on the swelling and drug‐released behaviors were studied. The results showed that, because of the hydrophobicity of the silyl group, the more silane monomers in the copolymeric hydrogels the lower was the swelling ratio of the gels. The hydrophobicity of the silyl group affected the swelling mechanism, which resulted from the non‐Fickian diffusion for the gels. The copolymeric gels clearly exhibited gel transition temperatures. The copolymeric hydrogels could be applied to a drug‐release and drug‐delivery system. The delivery amount would approach a steady state after three cycle operations of delivery. The gels also showed an on–off switch behavior on drug release depending on the temperature, and the gels released more CV with the gels in a swollen state. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 2523–2532, 2002     

Investigation of loading and release in PVA‐based hydrogels

We used Methylene Blue (MB) and Methyl Orange (MO) as model drugs to investigate the controlled release behavior of hydrogels from poly(vinyl alcohol) crosslinked with ethylenediaminetetraacetic dianhydride. The cationic or anionic character of these compounds and the molecular weight between crosslinks of the hydrogel and the concentration of ionizable groups in the hydrogel greatly affected the loading and release of the drugs. MB loading was favored, therefore, by a higher content of negative charges in the hydrogel, although this implied a greater degree of crosslinking and, therefore, a lower mesh size. On the other hand, the overall loading of negative MO, favored by a higher mesh size, was very low because of unfavorable interactions with the electrolyte charges. Release studies showed that one of the parameters that most affected the drug release behavior of these hydrogels was the pH of the solution. MB and MO were not completely released, even at pH 1. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 1644– 1651, 2002.     

Effect of montmorillonite on the swelling behavior and drug‐release behavior of nanocomposite hydrogels

A series of nanocomposite hydrogels were prepared from various ratios of N‐isopropylacrylamide (NIPAAm) and organic montmorillonite (MMT). The influence of the extent of MMT in the NIPAAm/MMT nanocomposite hydrogels on the physical properties and drug‐release behavior was the main purpose of this study. The microstructure and morphology were identified by X‐ray diffraction (XRD) and scanning electronic microscopy (SEM). The results showed that the swelling ratios for these nanocomposite hydrogels decreased with increase in the content of MMT. The gel strength and Young's modulus of the gels also increased with increase in the content of MMT. XRD results indicated that the exfoliation of MMT was achieved in the swollen state. Finally, the drug‐release behavior for the gels was also assessed. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3652–3660, 2003     

Cephazoline sodium release from poly(N‐isopropyl acrylamide‐co‐N,N‐dimethylacrylamide) hydrogels

Hydrogels are hydrophilic polymers that swell to an equilibrium volume in the presence of water, preserving their shape. The dynamic swelling behavior of poly(N‐isopropylacrylamide‐co‐N,N‐dimethylacrylamide) [poly(NIPA‐co‐DMA)] copolymers at 37°C was investigated. It was observed that the swelling degree in the copolymers decreases with the N‐isopropylacrylamide content. In addition, the liberation mechanism was found to be Fickian. Diffusion coefficients according to Fick′s law as a function of the N‐isopropylacrylamide concentration and results of the release process are reported. The kinetics of cephazoline sodium release from poly(NIPA‐co‐DMA) hydrogels with different compositions was studied. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 91: 3433–3437, 2004     

Electrically modulated transport of diclofenac salts through hydrogels of sodium alginate,carbopol, and their blend polymers

The electrically modulated transdermal migration of diclofenac sodium (DS), diclofenac potassium (DP), and diclofenac diethylammonium (DD) drugs from the hydrogels of sodium alginate (NaAlg), carbopol (CP), and blends of NaAlg with CP prepared in 2:1, 2:1.5, and 2:2 ratios was investigated. The release of DS, DP, and DD was investigated through excised rat skin to study the effects of viscosity, pH, and the ionic strength of the receptor medium under the influence of an electrical current in a switch‐on and switch‐off mode. A pulsatile pattern of transport was observed that depended on the presence or absence of an electrical current. Drug transport was dependent on the electrical current, the ionic nature of drugs, and the ionic strength of the diffusion medium. Drug transport followed the sequence DS > DP > DD. A decrease in viscosity and an increase in the pH of the hydrogel were observed when an electrical current was applied. CP was more responsive to an electrical stimulus, but the rate of transport was higher for NaAlg. Increasing the amount of CP in the blends increased the electrical responsiveness. The blend hydrogel with a high CP content showed the highest enhancement in drug transport, whereas the NaAlg hydrogel showed the least. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 301–311, 2005