Effect of attapulgite contents on release behaviors of a pH sensitive carboxymethyl cellulose‐g‐poly(acrylic acid)/attapulgite/sodium alginate composite hydrogel bead containing diclofenac

A series of pH‐sensitive composite hydrogel beads, carboxymethyl cellulose‐g‐poly(acrylic acid)/attapulgite/sodium alginate (CMC‐g‐PAA/APT/SA), were prepared by combining CMC‐g‐PAA/APT composite and SA, using Ca²⁺ as the ionic crosslinking agent and diclofenac sodium (DS) as the model drug. The effects of APT content and external pH on the swelling properties and release behaviors of DS from the composite hydrogel beads were investigated. The results showed that the composite hydrogel beads exhibited good pH‐sensitivity. Introducing 20% APT into CMC‐g‐PAA hydrogel could change the surface structure of the composite hydrogel beads, decrease the swelling ability, and relieve the burst release effect of DS. The drug cumulative release ratio of DS from the hydrogel beads in simulated gastric fluid was only 3.71% within 3 hour, but in simulated intestinal fluid about 50% for 3 hour, 85% for 12 hour, up to 90% after 24 hour. The obtained results indicated that the CMC‐g‐PAA/APT/SA hydrogel beads could be applied to the drug delivery system as drug carriers in the intestinal tract. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

载阿奇霉素-鼠李糖脂胶束制备工艺优化及性能表征

采用薄膜水化法制备载阿奇霉素-鼠李糖脂(AZI-RHL)胶束,以包封率、载药量为评价指标,通过单因素试验和正交试验优化制备工艺,并考察其理化性质。制备载药胶束前先测定RHL水溶液的临界胶束浓度(CMC)。结果表明,RHL水溶液的CMC值约为0.25 mg/mL。优化后的最佳制备工艺条件为：RHL投料量100 mg,甲醇用量12 mL,搅拌时长20 min。在此条件下制备的AZI-RHL胶束呈球形,水动力学直径为136.3±68.5 nm,Zeta电位为-23.1±6.8 mV,包封率为80.34%±0.60%,载药量为19.42%±0.48%。红外光谱证明AZI包埋在胶束中。体外释放试验表明AZI-RHL胶束具有一定的缓释作用,其体外累计释放曲线符合Ritger-Peppas方程,释放药物以Fick扩散为主。综上所述,AZI-RHL胶束的制备工艺稳定可靠,胶束粒径小,且包封率、载药量高,是一种有潜力的新型制剂。     

Drug‐delivery system based on core–shell‐type nanoparticles composed of poly(γ‐benzyl‐L‐glutamate) and poly(ethylene oxide)

A block copolymer based on poly(γ‐benzyl‐L ‐glutamate) (PBLG) as the hydrophobic part and poly(ethylene oxide) (PEO) as the hydrophilic part was synthesized and characterized. PBLG/PEO/PBLG (GEG) block copolymer nanoparticles were prepared using the dialysis technique. Fluorescence spectroscopy measurement suggested that GEG block copolymers were associated in water to form polymeric micelles and the critical micelle concentration (CMC) value of the GEG‐50 block copolymer was 0.0084 g/L. Particle‐size distribution of the GEG‐50 block copolymer based on the number average was 34.9 ± 17.6 nm. Also, the particle size and drug‐loading contents of GEG nanoparticles were significantly changed with the initial solvent used. From transmission electron microscope (TEM) observations, the GEG polymeric micelle was a nice spherical shape and the sizes ranged from approximately 20–60 nm in diameter. Results from assessing the drug‐loading contents against the initial solvent showed that the use of tetrahydrofuran (THF) or 1,4‐dioxane as the initial solvent resulted in higher drug‐loading contents than those of other solvents. In the drug‐release studies, the higher the molecular weight of the polymer and drug‐loading contents, the slower the drug release. Also, the initial solvent used was significantly affected not only in the drug‐loading contents but also in the drug‐release kinetics. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 75: 1115–1126, 2000     

Preparation of carbon dioxide/propylene oxide/ε-caprolactone copolymers and their drug release behaviors

Summary Poly (propylene-ram-ε-caprolactone carbonate) (PPCL) and poly (propylene carbonate) (PPC) were synthesized by ring-opening copolymerization from carbon dioxide, propylene oxide (PO) and ε-caprolactone (CL) using a polymer-supported bimetallic complexes (PBM) as catalyst. PPC and PPCL microspheres containing a 5-alpha reductase inhibitor, finasteride were elaborated by a conventional oil-in-water (O/W) emulsion-solvent evaporation method. The effects of polymer used on microspheres morphology, size, drug loading, encapsulation efficiency and drug release behaviors were examined. In vitro drug release of these microcapsules was performed in a pH 7.4 phosphate-buffered solution. A prolonged in vitro drug release profile was observed. The release profiles of finasteride from PPC and PPCL microcapsules were found to occur with a burst release followed by a gradual release phase. Drug release rates were dependent upon the properties of the polymer in the microspheres, the higher hydrolytic activity of polymer provided faster release rate.     

Preparation and characterization of tetracycline‐loaded interpenetrating polymer networks of carboxymethyl cellulose and poly(acrylic acid): water sorption and drug release study

Tetracycline (TC)‐loaded ionic interpenetrating polymer networks (IPNs) of carboxymethyl cellulose (CMC) and crosslinked poly(acrylic acid) (PAA) were prepared and characterized by infrared spectral analysis, differential scanning calorimetry and scanning electron microscopy techniques. The prepared IPNs were evaluated for in vitro blood compatibility by clot formation and hemolysis methods and their water imbibitions capacity was determined. Fractional release dynamics of tetracycline was also investigated from loaded IPNs of CMC and PAA. The entrapped drug was examined for antibacterial activity and structural integrity and effects of various parameters such as percentage loading of the drug, chemical composition of the carrier IPN, pH and temperature of the release medium were investigated on the release profiles of TC. The drug was also released in different simulated biological fluids. Copyright © 2005 Society of Chemical Industry     

Cu2O光催化剂综述

介绍Cu_2O光催化降解机理,禁带宽度,光生载流子利用率和溶液pH影响Cu_2O光催化降解活性,通过掺杂,负载贵金属,碳材料修饰和半导体复合可提高Cu_2O光催化性能。     

O-季铵化-N-(4-十二烷氧基)壳聚糖苯甲醛席夫碱的制备及胶束pH响应性

制备双亲性的O-季铵化-N-(4-十二烷氧基)壳聚糖苯甲醛席夫碱(QA-CS-DBA),采用FTIR、¹H NMR及元素分析对产物进行表征。通过超声法制备QA-CS-DBA载酮洛芬胶束,考察胶束的临界胶束浓度、粒径、Zeta电位、载药量和包封率,并对胶束在不同pH值条件下的药物释放行为及Zeta电位变化进行研究。结果表明,QA-CS-DBA能将酮洛芬包载于胶束疏水内核,载药量为39.37%,包封率为46.04%,载药胶束粒径为341nm,Zeta电位为30.8mV。胶束Zeta电位及载药胶束的药物释放行为具有pH响应性。     

叶面亲和型阿维菌素微胶囊的制备及pH响应性释放性能

为减少农药流失,设计了一种叶面亲和型缓释微胶囊。以甲基丙烯酸甲酯（MMA）接枝改性羧甲基纤维素（CMC）得到羧甲基纤维素-聚甲基丙烯酸甲酯（CMC-g-PMMA）,然后利用自组装负载阿维菌素（AVM）形成载药微胶囊（CMC-g-PMMA@AVM）,通过多巴胺（DA）包覆提高CMC-g-PMMA@AVM的叶面亲和性。采用扫描电镜、红外光谱、热重分析等对其结构和形貌进行表征,研究了微胶囊的载药性能、叶面亲和性及响应释放性能。结果显示,DA/CMC-g-PMMA@AVM为平均粒径126nm的球形粒子,多巴胺的包覆可有效提高微胶囊的载药性能,包封率可达88.56%;增强AVM的叶面亲和性,使其叶面滞留量相对于阿维菌素水乳液提升30.56%;赋予AVM优异的抗紫外光分解性能,强紫外光照射60min后,由AVM水乳液中AVM的残留率14.03%提高到DA/CMC-g-PMMA@AVM中的59.55%。载药微胶囊中药物释放具有pH响应,在pH=5条件下出现爆释,药物释放过程符合Weibull模型,受Fick扩散控制。     

pH-响应型K5多糖药物传递系统的构建及应用

化学疗法是目前癌症治疗的主要方法,但目前常用的化疗药物却普遍存在水溶性不佳、缺乏选择性、毒副作用大等不足,而限制了其应用。本研究基于肝素前体K5多糖为模板,利用具有pH响应性的硼酸酯键,构建了K5-脱氧胆酸（K5AD）两亲性药物传递系统,用于阿霉素（doxorubicin,DOX）的靶向传递释放。考察了该体系的体外药物释放行为,并在体外评价其对肿瘤细胞的抑制作用。结果表明,K5AD的临界胶束浓度值为23.5mg/L,在水溶液中能自组装形成平均粒径为196.7nm的胶束;K5AD-DOX体外药物释放实验显示其具有pH-响应的释药行为,在pH 5.0的酸性环境下药物释放速率较pH 7.4下更快。细胞实验表明,K5AD-DOX对肿瘤细胞的毒性远大于对正常细胞的毒性,表现出治疗的选择性。     

Radiation Synthesis of pH-Sensitive Hydrogels From Carboxymethyl Cellulose/Poly(ethylene Oxide) Blends as Drug Delivery Systems

Gamma irradiation was used to prepare hydrogels from carboxymethyl cellulose (CMC) and poly(ethylene oxide) (PEO) blends in the form of films. The hydrogels were characterized by IR spectroscopy, differential scanning calorimetry, thermogravimetric analysis, mechanical testing, and scanning electron microscopy. The swelling in different buffers of different pH values was also studied. The results indicated the formation of network structure and that the swelling of hydrogels is thermo- and pH-sensitive. The CMC/PEO hydrogels were evaluated for the possible use in drug delivery field, in which the release profile of ketoprofen, as a drug model was investigated.     

Complexation Hydrogels for the Oral Delivery of Growth Hormone and Salmon Calcitonin

The hydrogel system of poly(methacrylic acid-co-N-vinyl pyrrolidone) was evaluated for use as an oral delivery system for growth hormone and salmon calcitonin. These proteins were selected because of their therapeutic importance and the insight provided by evaluating the delivery of a therapeutic agent with a high molecular weight (growth hormone) and a drug with a high isoelectric point (salmon calcitonin). Growth hormone loading and release studies were performed for both P(MAA-co-NVP) and P(MAA-g-PEG). Loading efficiencies for the respective systems were 50.9 ± 1.8% and 57.8 ± 4.1%; weight incorporation of the protein was determined to be 3.5 ± 0.1% and 4.0 ± 0.3%. At pH 7.4, growth hormone release of 90% occurred within 45 min for P(MAA-co-NVP) microparticles; 90% release was not achieved with P(MAA-g-PEG) microparticles until 180 min. At pH 1.2, no release occurred from P(MAA-co-NVP) microparticles but 10% release occurred from P(MAA-g-PEG) microparticles. Salmon calcitonin loading and release were shown to be affected by the negative charges of deprotonated MAA; for systems with monomer molar feed ratios of 4:1, 1:1 and 1:4 MAA:NVP, loading efficiencies were determined to be 70.6 ± 3.0%, 25.3 ± 1.2%, and 1.6 ± 1.3%. Salmon calcitonin release was minimal from the copolymer with 4:1 MAA:NVP monomer feed at pH 7.4. The release improved when the pH was raised above physiological levels. These studies confirmed that P(MAA-co-NVP) was an effective oral delivery system for high molecular weight drugs, but improvements are needed before the system could be utilized for high isoelectric point therapeutic delivery.     

Carboxylmethylcellulose/bentonite composite gels: Water sorption behavior and controlled release of herbicide

The composite gels were prepared by adding bentonite or its acid‐activated derivative into the carboxylmethylcellulose (CMC) gel, and the resulted products were characterized with infrared spectroscopy. Different from ordinary swellable hydrogels, the CMC/bentonite hydrogel beads shrinked in water. The water sorption of dried gels was limited below 120% of their own weight, and a sorption equilibrium reached quickly within 20–40 min. The water of swollen gels exists mainly in bound status according to the DSC analysis. The release experiments in water were carried out to evaluate the release of herbicide metolachlor from gel formulations. The release mechanism dominated by a Fickian diffusion might be related to the quick and limited swelling of dried gels. Addition of bentonites in CMC gel is beneficial for slowing the release of metolachlor, especially when the acid‐activated bentonite was added. The time taken for 50% of metolachlor to be released, t₅₀ was prolonged to 158 h for the composite gel formulation based on acid‐activated bentonite from the 61.1 h for pure CMC gel formulation. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

生物可降解两亲性嵌段共聚物胶束的制备及其对叶酸的控制释放

以甲氧基聚乙二醇(mPEG)为引发剂,在辛酸亚锡催化下引发ε-环己内酯(CL)开环聚合,合成了聚乙二醇-聚己内酯两亲性嵌段共聚物(mPEG-PCL)。通过FTIR、1H-NMR及GPC等表征手段确定了mPEG-PCL的组成及结构。采用芘荧光探针法、透射电镜和动态激光光散射研究了聚合物在水中的自组装行为。结果表明:聚合物在水溶液中能够自组装形成粒径小于100 nm的规则球状胶束,且具有较低的临界胶束浓度(7.35×10-3 g/L);模型药物(叶酸)成功负载于聚合物纳米胶束内,并且能延缓叶酸的释放,其释药速率受载药量和释放介质pH的影响。     

Magnetic and electric responsive hydrogel–magnetic nanocomposites for drug‐delivery application

Magnetic and electrically responsive hydrogel networks were developed for drug‐delivery applications. The hydrogel matrices were synthesized by the polymerization of acrylamide monomer in the presence of carboxymethylcellulose (CMC) or methylcellulose (MC) with N,N‐methylenebisacrylamide, a crosslinker with the redox initiating system ammonium persulfate/tetramethylethylenediamine. The magnetic nanoparticles were generated throughout these hydrogel matrices by an in situ method by the incorporation of iron ions and their subsequent reduction with ammonia. A series of hydrogel–magnetic nanocomposites (HGMNCs) were developed with various CMC and MC compositions. The synthesized HGMNCs were characterized with spectral (Fourier transform infrared and ultraviolet–visible spectroscopy), X‐ray diffraction, thermal, and microscopy methods. These HGMNCs contained iron oxide (Fe₃O₄) nanoparticles with an average particle size of about 22 nm, as observed by transmission electron microscopy. The dielectrical properties of the pure hydrogel (HG); the hydrogel loaded with iron ions, or the hydrogel iron‐ion composite (HGIC); and the HGMNCs were measured. These results suggest that HGMNCs exhibited higher dielectric constants compared to HG and HGICs. The curcumin loading and release characteristics were also measured for HG, HGIC, and HGMNC systems. These data revealed that there was a sustained release of curcumin from HGMNCs because of the presence of magnetic nanoparticles in the hydrogel networks. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

P(HEMA-co-NVP)/CMC的制备及对药物的控制释放

用N,N-亚甲基双丙烯酰胺(Bis)为交联剂,过硫酸铵(APS)为引发剂,羧甲基纤维素(CMC)为助剂,合成了N-乙烯基吡咯烷酮与甲基丙烯酸-β羟基乙酯共聚物[P(NVP-co-HEMA)]/CMC半互穿网络水凝胶,并在模拟人体环境的条件下,以非水溶性药物萘普生为模拟药物,考察了水凝胶在不同温度及酸度下的药物释放。非水溶性药物萘普生在P(HE-MA-co-NVP)/CMC半互穿网络水凝胶载体体系中pH为2.00时,药物释放率受温度的影响较少,而在pH为7.40时,药物释放率受温度的影响较大。     

Alginate/carboxymethyl chitosan composite gel beads for oral drug delivery

This paper reports the synthesis of pH-sensitive gel beads derived from alginate (SA) and carboxymethyl chitosan (CMCS) for drug delivery. The composite SA/CMCS gel beads were prepared by dual ionic gelation: one ionic gelation between SA and Ca²⁺ and another one between CMCS and β-Sodium glycerophosphate (β-GP). The structure properties of hydrogel beads were characterized by SEM, IR and TG technique. The influence of the polymer composition and cross-linkers on the gel swelling property was investigated. When the concentration of CMCS and SA were 3 % and the volume ratio was 1:2, the swelling rate of gel beads crosslinked by β-GP and CaCl₂ solution can increase up to 31.2 and the swelling time can reach 10.5 h. In the drug release study, bovine serum albumin (BSA) was chosen as model drugs. The results indicated that BSA released slowly from the gel beads at pH 1.2 and the release ratio was about 10 %. At pH 7.4, the amounts of BSA released increased significantly as compared to those released at pH 1.2 and the total release time was extended to 11 h. The composite gel system demonstrates sustained release profile and pH sensitivity, which can be considered as good candidates for oral drug delivery systems.     

Calcium‐carboxymethyl chitosan hydrogel beads for protein drug delivery system

In this study, carboxymethyl chitosan (CMC) hydrogel beads were prepared by crosslinking with Ca²⁺. The pH‐sensitive characteristics of the beads were investigated by simulating gastrointestinal pH conditions. As a potential protein drug delivery system, the beads were loaded with a model protein (bovine serum albumin, BSA). To improve the entrapment efficiency of BSA, the beads were further coated with a chitosan/CMC polyelectrolyte complex (PEC) membrane by extruding a CMC/BSA solution into a CaCl₂/chitosan gelation medium. Finally, the release studies of BSA‐loaded beads were conducted. We found that, the maximum swelling ratios of the beads at pH 7.4 (17–21) were much higher than those at pH 1.2 (2–2.5). Higher entrapment efficiency (73.2%) was achieved in the chitosan‐coated calcium‐CMC beads, compared with that (44.4%) in the bare calcium‐CMC beads. The PEC membrane limited the BSA release, while the final disintegration of beads at pH 7.4 still leaded to a full BSA release. Therefore, the chitosan‐coated calcium‐CMC hydrogel beads with higher entrapment efficiency and proper protein release properties were a promising protein drug carrier for the site‐specific release in the intestine. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3164–3168, 2007     

Photo-swing extraction system for lanthanide separation by a thermosensitive polymer gel combined with carbon nanotubes

A novel photo-swing extraction system for lanthanide separation was developed using an acid phosphoxy ethyl methacrylate (Phosmer-M) copolymerized thermosensitive polymer gel and N-isopropylacrylamide (NIPAM) combined with single-walled carbon nanotubes (CNTs) as the extracting material. The swelling and shrinking phase transition of the Phosmer-M/NIPAM/CNT gel was successfully induced by photo-irradiation with a halogen lamp because of the heat generation by the CNTs, which occurred upon visible light absorption. The extraction ability of Eu(III) increased upon photo-irradiation because of changes in the volume and hydrophobicity of the composite gel. The ratio of the distribution coefficient with and without photo-irradiation (K_dphoto/K_d25) increased with an increase in the pH. The composite gel possessed sufficient loading and release capacities for Eu(III), La(III) and Lu(III) in repeated processes after photo-irradiation. The selectivity for Eu(III) over La(III) in binary metal systems increased due to photo-irradiation because the observed improvement in the extraction of Eu(III) was greater than that of La(III) during the phase transition of the gel.     

A Novel Carbon Dots/Thermo-Sensitive In Situ Gel for a Composite Ocular Drug Delivery System: Characterization,Ex-Vivo Imaging,and In Vivo Evaluation

We developed a potential composite ocular drug delivery system for the topical administration of diclofenac sodium (DS). The novel carbon dot CD_C-HP was synthesized by the pyrolysis of hyaluronic acid and carboxymethyl chitosan through a one-step hydrothermal method and then embedded in a thermosensitive in situ gel of poloxamer 407 and poloxamer 188 through swelling loading. The physicochemical characteristics of these carbon dots were investigated. The results of the in vitro release test showed that this composite ocular drug delivery system (DS-CD_C-HP-Gel) exhibited sustained release for 12 h. The study of the ex vivo fluorescence distribution in ocular tissues showed that it could be used for bioimaging and tracing in ocular tissues and prolong precorneal retention. Elimination profiles in tears corresponded to the study of ex vivo fluorescence imaging. The area under the curve of DS in the aqueous humor in the DS-CD_C-HP-Gel group was 3.45-fold that in the DS eye drops group, indicating a longer precorneal retention time. DS-CD_C-HP with a positive charge and combined with a thermosensitive in situ gel might strengthen adherence to the corneal surface and prolong the ocular surface retention time to improve the bioavailability. This composite ocular delivery system possesses potential applications in ocular imaging and drug delivery.     

右旋布洛芬/盐酸改性蒙脱土的制备及体外释放研究

目的：以酸改性蒙脱土为药物载体,制备右旋布洛芬/酸改性蒙脱土复合物,提高右旋布洛芬的载药量,并探索载药复合物在不同释放介质中的释放规律。方法：首先用浓度为5%~20%的盐酸对蒙脱土进行预处理,利用X-射线衍射（XRD）、比表面积测定（BET）、扫面电子显微镜（SEM）等表征方法对蒙脱土进行结构表征,筛选最佳酸处理浓度;然后用溶液插层法将右旋布洛芬负载于酸化后的蒙脱土上,制得右旋布洛芬/酸改性蒙脱土复合物;采用透析法对右旋布洛芬/酸改性蒙脱土复合体系进行体外释放实验。结果：经酸改性后蒙脱土的结构发生改变,当酸浓度为15%时,蒙脱土的比表面积达到最大值246 m2/g。上载右旋布洛芬后,载药量最大可达352.4 mg/g。体外释放实验表明,右旋布洛芬/酸改性蒙脱土的累积释药百分量受pH的影响,当pH为1.2时,其累积释药百分量为18.6%,当pH为6.8时,则为89.3%。结论：盐酸改性蒙脱土有助于提高药物的负载量,右旋布洛芬/酸改性蒙脱土复合物具有良好的缓释作用并有一定的pH响应性,有望制成肠道缓释口服药物制剂。