Efficient loading and delivery of ciprofloxacin by smart alginate/carboxylated graphene oxide/aminated chitosan composite microbeads: In vitro release and kinetic studies

New composite microbeads were formulated as smart pH-sensitive vehicle for efficient delivery of ciprofloxacin (CIP) drug. Herein, carboxylated graphene oxide (CGO) was successfully impregnated into alginate (Alg) microbeads, which were then coated with aminated chitosan (AmCs) layer to form core–shell Alg/CGO@AmCs composite microbeads. Diverse analysis tools comprising FTIR, TGA, XRD and SEM were employed to characterize the developed carriers, while their swelling profiles and pH-sensitivity were examined under different pHs. The results clarified that increasing CGO and AmCs concentrations in microbeads matrix greatly protected Alg microbeads from fast disintegration at colon pH and prolonged their swelling time. Moreover, about 94.65 % of CIP drug was successfully loaded by Alg/CGO@AmCs composite microbeads compared to 61.95 % for Alg microbeads, confirming their reduced porosity. The in vitro CIP-release profiles were investigated in simulated gastrointestinal conditions. Furthermore, increasing AmCs concentration in the outer shell of composite microbeads clearly minimized the CIP burst release at the colon region and offered a sustained release performance. Besides, the CIP release mechanism was well-described by korsmeyer-peppas kinetic model. The cytotoxicity study confirmed the potential safety of the Alg/CGO@AmCs composite microbeads with human cell viability reached 98.98 %, suggesting their applicability as smart carriers for oral delivery of antibiotics.     

Effect of Different Crosslinking Strategies on Physical Properties and Biocompatibility of Freestanding Multilayer Films Made of Alginate and Chitosan

Freestanding multilayer films prepared by layer‐by‐layer technique have attracted interest as promising materials for wound dressings. The goal is to fabricate freestanding films using chitosan (CHI) and alginate (ALG) including subsequent crosslinking to improve the mechanical properties of films while maintaining their biocompatibility. Three crosslinking strategies are investigated, namely use of calcium ions for crosslinking ALG, 1‐ethyl‐3‐(‐3‐dimethylaminopropyl) carbodiimide combined with N‐hydroxysuccinimide for crosslinking ALG with CHI, and Genipin for crosslinking chitosan inside the films. Different characteristics, such as surface morphology, wettability, swelling, roughness, and mechanical properties are investigated showing that films became thinner, exhibited rougher surfaces, had lower water uptake, and increased mechanical strength after crosslinking. Changes of wettability are moderate and dependent on the crosslinking method. In vitro cytotoxicity and cell attachment studies with human dermal fibroblasts show that freestanding CHI‐ALG films represent a poorly adhesive substratum for fibroblasts, while studies using incubation of plastic‐adherent fibroblast beneath floating films show no signs of cytotoxicity in a time frame of 7 days. Results from cell experiments combined with film characteristics after crosslinking, indicate that crosslinked freestanding films made of ALG and CHI may be interesting candidates for wound dressings.     

Controlled release of dual drugs from emulsion electrospun nanofibrous mats

The purpose of this work is to develop a novel type of tissue engineering scaffold or drugs delivery carrier with the capability of encapsulation and controlled release drugs. In this study, Rhodamine B and Bovine Serum Albumin (BSA) were successfully incorporated into nanofibers by means of emulsion electrospinning. The morphology of composite nanofibers was studied by Scanning Electron Microscopy (SEM). The composite nanofibrous mats made from emulsion electrospinning were characterized by water contact angle measurement and X-ray diffraction. In vitro dual drugs release behaviors from composite nanofibrous mats were investigated. The results indicated that the incorporated drug and/or proteins in composite fibrous mats made from electrospinning could be control released by adjusting the processes of emulsions preparation.     

Chondroitin Sulfate Fluorescence Biosensor Based on Graphere Quantum Dots Aggregating on CMC/CS Polyelectrolyte Microspheres

Here, we report an efficient fluorescence biosensor for chondroitin sulfate(CHS) based on polyelectrolyte microspheres of carboxymethyl cellulose(CMC) and chitosan(CS) composites inducing the aggregation of graphene quantum dots(GQDs), calling CMC/CS-GQDs. The polyelectrolyte microspheres(CMC/CS microspheres) were fabricated by using anioniccationic electrostatic attraction between CMC and CS by high voltage electrostatic spray technology. The aggregating process of GQDs was based on the anionic-cationic electrostatic attraction as well. After combing with the polyelectrolyte microspheres, the fluorescence of GQDs disappeared. CHS, which widely consists in the cell surface of human beings and animals, carries a large number of negative charges on the surface. The addition of CHS enabled CHS and GQDs to compete with each other to composite with the CMC/CS microshpheres. As a result of the higher surface charge density of CHS, CMC/CS-CHS formed accompanied by the release of GQDs, and the fluorescence of the system recovered. The CHS content was detected by analyzing the system's fluorescence recovery, which suggested that the obtained fluorescence biosensor can accurately detect the concentration of CHS. The test results showed that the linear range of the fluorescence recovery for this biosensor with respect to CHS was 0~12.00 mg/mL, and the detection limit was 10-8 M. Besides, to test the stability of the biosensor, the CMC/CS-GQDs micropsheres persisted for one month, with a low fluorescence quenching of 9.48%. These results suggested that CMC/CS-GQDs can be utilized as efficient fluorescence biosensor for the detection of CHS. Moreover, the detection method was simple and efficient, and could be widely popularized.     

Defoliation and plasmid delivery with layer-by-layer coated colloids

The uptake of polyelectrolyte multilayer coated colloids into cells, subsequent defoliation and plasmid delivery was studied by means of confocal microscopy and flow cytometry. Silica particles coated layer-wise with protamine and dextran sulfate were given to HEK 293T cells. Optimum uptake was found with protamine as the top layer. The particle uptake likely follows an non-receptor-mediated endocytotic pathway. Defoliation of polyelectrolyte multilayer coated particles within cells was demonstrated by the release of incorporated plasmids as indicated by the expression of plasmid encoded proteins using the enhanced green fluorescence proteine (pEGFP-C1) plasmid and a red fluorescence protein (pDsRed1-N1) plasmid. This proves, together with the direct observation of fluorescent layer debris, the defoliation of coated particles and the release of layer components into the cytoplasm. Particle uptake and GFP expression.     

复合催化剂α-(Fe，Cu)OOH/RGO的制备、表征及其协同H2O2在可见光下去除环丙沙星性能

采用一步回流法制备了α-(Fe,Cu)OOH/RGO复合催化剂,通过粉末X射线衍射、扫描电子显微镜和X射线光电子能谱等对催化剂进行了表征,并以30 mg·L^-1的环丙沙星(CIP)为目标污染物,研究了不同制备条件下所得催化剂在可见光照射下协同H2O2对CIP的去除效果。结果表明,成功实现了α-(Fe,Cu)OOH纳米棒在石墨烯二维薄片上原位生长,α-(Fe,Cu)OOH/RGO复合材料的可见光吸收边发生红移,禁带宽度从2.02 eV变为1.76 eV。石墨烯复合不但增强了对污染物的吸附能力,而且加快了光生电子的分离、迁移速率,还提高了反应体系中电子的传导效率。当石墨烯复合比例(质量分数)为1%时,复合催化剂的催化性能最佳。当催化剂投加量为0.40 g·L^-1,H2O2浓度为0.10 mol·L^-1时,反应120 min,CIP被全部去除。α-(Fe,Cu)OOH/RGO循环使用5次,对CIP的去除率均在90%以上,表明催化剂具有较强的催化活性和较好的稳定性。     

具有抗菌性能的载药复合微纳米纤维的制备及其结构和性能表征

利用静电纺丝技术制备了一种具有抗菌性能的氧化锌(ZnO)/聚乳酸(PLA)/聚己内酯(PCL)载药微纳米纤维膜,并通过扫描电子显微镜(SEM)、X射线衍射(XRD)和傅里叶变换红外光谱(FTIR)分别对复合膜的表面形态、元素组成和化学结构进行表征。通过抗菌实验评价了复合膜的抗菌性能,用紫外分光光度计测试复合膜在体外的药物释放行为。结果显示,以物理共混的方式将ZnO和氢溴酸高乌甲素(LAH)成功载入复合微纳米纤维;与PLA/PCL复合微纳米纤维膜相比,ZnO/PLA/PCL复合微纳米纤维膜表现出更好的抗菌效率。当ZnO含量为10%(wt)时,复合微纳米纤维膜具有最佳的抗菌性能;药物释放性能结果表明,ZnO/PLA/PCL复合微纳米纤维膜具有良好的药物缓释性能。     

Side effect reduction of encapsulated hydrocortisone crystals by insulin/alginate shells

Insulin/alginate (ALG) microcapsules for controllable release and side effect reduction of a glucocorticoid have been fabricated via the layer-by-layer (LbL) assembly technique. Insulin and ALG are deposited alternately onto hydrocortisone (HC) crystals to form a core-shell structure. This insulin/ALG microcapsule can prolong the release of HC under physical conditions and control the HC release rate by adjusting the number of insulin/ALG bilayers adsorbed onto HC crystals. The release of insulin from the capsule wall exhibits a little lag, compared with that of the HC. It is a great advantage for this system because hyperglycemia caused by HC usually arises a few hours after its administration, which could be inhibited by the delayed release of insulin from the shell of the microcapsule. This synergy effect might enable a new way of using one carrier to deliver two kinds of drugs and reduce their side effects at the same time.     

Preparation and characterization of mono-valent ion selective polypyrrole composite ion-exchange membranes

Polypyrrole composite cation- and anion-exchange membranes (CEM and AEM), in which polypyrrole (PPY) coated on one surface of the membrane as a thin layer, were prepared by chemical polymerization of pyrrole in the presence of high oxidant concentration (Na₂S₂O₈). Existence of polypyrrole layer on the both types of ion-exchange membranes were confirmed by recording their coating density, SEM images and conductivity. These membranes were extensively characterized by recording their properties such as water uptake, ion-exchange capacity, contact angle, permselectivity and membrane conductivity as a function of polymerization time such as. It was observed that due to coating of PPY for 2 h, membrane permselectivity of CEM for NaCl (0.907) was reduced to 0.873, while it was increased from 0.747 to 0.889 in the case of AEM. Similar behaviors were also obtained for bi-valent electrolytes. Electrodialysis experiments were also conducted with polypyrrole composite ion-exchange membranes using mixed electrolytic systems. Relative dialytic rates for NaCl with respect to other bi-valent electrolyte were varied in between 5 and 8 (depending on bi-valent electrolyte), which suggested the feasible and efficient separation of mono-valent from bi-valent electrolyte. Slower electro-migration of bi-valent electrolyte (CaCl₂, MgCl₂ and CuCl₂) in comparison to NaCl was explained on the basis of synergetic effect of sieving of bulkier bi-valent cations by tight and rigid polypyrrole layer and the difference in electrostatic and hydrophobic–hydrophilic repulsion force between bi-valent cations and mono-valent cation. It was concluded that these composite membranes are suitable for the efficient separation of same type of charged ions by electro-driven separation techniques.     

Modulation of Tenoxicam release from hydrophilic matrix: modulator membrane versus rate-controlling membrane

This paper describes the preparation of two layered device comprising of tenoxicam containing layer and a drug free membrane layer based on Geomatrix Technology. Our device based on bilaminated films which produced by a casting/solvent evaporation technique. The drug-hydroxypropyl methylcellulose (HPMC) layer was covered by drug free membrane layer composed of a mixture of different ratios of HPMC and ethyl cellulose (EC). The prepared devices were evaluated for thickness, weight, drug content uniformity, water absorption capacity and in-vitro drug release. The films were also evaluated for appearance, smoothness and transparency. The influence of drug free membrane layer composition and thickness on the drug release pattern was studied on 12 devices (D1 to D12). The results indicate that, the release of drug from HPMC matrixes without the drug free membrane layer was fast and follows diffusion controlled mechanism. The release of drug from the devices D1, D4, D9 and D12 follow the same mechanism, while the release of drug from other devices become linear with time (zero order) and extended for long time especially when thickness and the ratio of EC was increased in the drug free membrane layer. From this study it is concluded that, changing the geometry of drug layer by addition of drug free membrane layer and changing its composition and thickness plays an important role in determining whether the drug free membrane layer is rate-controlling or modulator membrane. Hence it can facilitate the development of different pharmaceutical products with different release pattern.     

利用升华物质2,4,6-三异丙基-1,3,5-三氧杂环己烷作模板剂制备聚苯胺包覆的中空硫电极材料

本文首次提出采用升华物质为模板,制备聚苯胺包覆的中空硫电极材料. 首先通过Na₂S₂O₃和稀HCl反应,在具有升华特性的ADD(2,4,6-三异丙基-1,3,5-三氧杂环己烷)微粒表面沉积一层S,然后在S的表面再沉积聚苯胺包覆层. 在经60 ^oC干燥12小时后,其中的ADD自然挥发,得到聚苯胺壳体包覆的中空硫复合物. SEM、TEM和TG分析表明,制得的聚苯胺包覆中空硫的粒径约为2 μm,硫含量为61.1%. 在500 mA·g^-1充放电电流下,首次放电比容量为776.2 mAh·g^-1,库仑效率为95.9%. 100次充放电循环后,放电比容量为524.7 mAh·g^-1. 由于聚苯胺包覆物的聚苯胺膜具有抑制聚硫锂向外的扩散作用,以及包覆物中的空间对放电时S的膨胀具有缓冲作用,聚苯胺包覆中空硫粉末的放电比容量和充放电稳定性均明显高于未包覆聚苯胺的中空硫和化学制备的硫. 这种制备导电聚合物包覆中空硫的新方法具有操作简单、成本低廉的优点,有进一步发展的前景.     

In vitro drug release from silicone rubber–polyacrylamide composite

Composite materials containing drugs were prepared from silicone rubber and hydrogel. Cross linked polyacrylamide (PAAm) hydrogel particles were incorporated into a silicone rubber to enhance the hydrophilicity and drug release capacity of silicone rubber as a matrix. Progesterone and Thymol Blue were used as a hydrophobic and hydrophilic drug model, respectively. Different amounts of polyacrylamide (PAAm) were mixed with the drugs and uncured silicone rubber at room temperature. The composite matrices were formed using a compression molding press and cured by thermal and γ-irradiation curing methods. In vitro drug release behavior of composites and their physical and mechanical properties were investigated. The results indicated that the hydrophilic character of silicone rubber was more pronounced with increasing the amount of PAAm. Also, a significant effect on the drug release profiles was observed. The γ-irradiation curing method improved mechanical properties of composites and affected the drug release profiles. It was found that the amounts of released progesterone from γ-irradiated samples increased in comparison with the thermally cross linked composite since released Thymol Blue was reduced.     

Sulfonated poly(ether ether ketone)/polyaniline composite proton-exchange membrane

Sulfonated poly(ether ether ketone) (PEEK) was prepared by sulfonation of commercial Victrex^@ PEEK and degree of sulfonation was found to be about 44.5% by ¹H NMR. Sulfonated PEEK/polyaniline composite membranes, in order to prevent methanol crossover, were prepared by chemical polymerization of a thin layer of polyaniline (PANI) in the presence of a high oxidant concentration on a single face modification. FTIR and PANI coating density studies confirmed the loading of PANI in sulfonated PEEK membrane matrix. PANI composite membranes with different polymerization time were prepared and subjected to thermogravimetric analysis as well as electrochemical and methanol permeability study to compare with sulfonated PEEK and Nafion 117 membrane. Ion-exchange capacity, water uptake, proton transport numbers and proton conductivities for different PANI composite sulfonated PEEK (SPEEK) membranes were found to be dependent on the coating density of the PANI in the membrane matrix and were slightly lower than that of Nafion 117 membrane. Methanol permeability of these membranes (especially SPEEK/PANI-1.5) was about four times lower than Nafion 117 membrane. Among the all SPEEK membranes synthesized in this study, SPEEK-1.5 appears to be more suitable for direct methanol fuel cell (DMFC) application considering optimum physicochemical and electrochemical properties, thermal stability as well as very low methanol permeability. Above all, the cost-effective and simple fabrication technique involved in the synthesis of such composite membranes makes their applicability quite attractive.     

酮洛芬/酸改性蒙脱土缓释体系的制备及体外释药研究

以盐酸改性蒙脱土为药物载体,采用离子交换法制备了酮洛芬/酸改性蒙脱土(KPF/acid-MMT)复合物.借助X射线衍射(XRD)、比表面积分析和扫描电子显微镜(SEM)等手段对复合物进行了结构表征;采用透析法研究了介质pH值对KPF/acid-MMT释放性能的影响;运用3种数学模型对其体外释放行为进行拟合.结果表明:经酸改性后,蒙脱土的比表面积由19.66 m~2/g增加到202.84 m~2/g,载药量由18.09%提高到37.24%;在人工模拟胃液(pH=1.2)和人工模拟肠液(pH=6.8)中,酮洛芬的累积释放量分别为18.6%和86.7%;零级动力学模型能更好地拟合和描述KPF/acid-MMT在人工模拟肠液中的体外释放行为.酸改性蒙脱土能有效提高药物的负载量,KPF/acid-MMT可实现药物的定向释放和缓释性能,有望制成肠道缓释口服药物制剂.     

Chitosan-based solid electrolyte composite membranes: I. Preparation and characterization

Some chitosan-based solid electrolyte composite membranes were prepared by incorporating potassium hydroxide as the functional ionic source, using glutaraldehyde as cross-linking agent. A three-layer structure with a porous intermediate layer for each composite membrane was observed using SEM. It was found that the concentration of potassium hydroxide solution used to prepare the composite membranes largely influenced the pore volume, porosity, pore size of the intermediate layer, as well as determined the content of potassium hydroxide inside the composite membranes, whereas the degree of cross-linking of composite membrane did not show notable effects. All composite membranes showed significant decreases in both their T_g and onset thermal degradation temperatures with respect to the solid cross-linked chitosan membranes without containing potassium hydroxide. Potassium hydroxide was found to be located inside the intermediate layer of composite membranes with shapes of bulky or fabric crystals. The crystalline properties of matrices of the composite membranes themselves were remarkably modified after being incorporated with potassium hydroxide and main crystalline peaks of matrices almost disappeared for all composite membranes.     

PREPARATION AND CHARACTERIZATION OF ION EXCHANGE MEMBRANES BASED ON POLYVINYLIDENE FLUORIDE

A new ion exchange membrane based on polyvinylidene fluoride (PVDF) and sulfonated poly(styrenedivinylbenzene) was prepared by in-situ polymerization. The incorporation of sulfonic groups into the polyvinylidene fluoride composite membrane was confirmed by infrared spectroscopy (IR), ion exchange capacity (IEC) and energy dispersive X-ray analysis (EDAX). Area resistance, IEC and water uptake of the treated membrane were evaluated. When area resistance in NaCl aqueous solution at 25℃, IEC is as high as 2.43 millimoles per gram of the wet membrane. The hydrophilicity of PVDF membrane is also significantly improved after treatment. When 60% of crosslinked membrane was sulfonated at 80℃ for 6 h, water uptake of the treated membrane can attain 64.7%.     

Hepatic-targeting microcapsules construction by self-assembly of bioactive galactose-branched polyelectrolyte for controlled drug release system

We describe the construction of hepatic-targeting microcapsules by self-assembly of chemo-enzymatic synthesized poly(vinyl galactose ester-co-methacryloxyethyl trimethylammonium chloride) (PGEDMC) containing galactose branches, which can be specifically recognized by membrane bound galactose receptors (ASGPR), for acyclovir (ACV) controlled release system. Alternate deposition of PGEDMC and poly(sodium 4-styrenesulfonate) (PSS) was carried out on ACV microcrystals. It was revealed that the drug release rate decreases with the increase of coated layer number and a microcapsule-drying treatment would enhance the sustained release effect probably because of a multilayer shrink and tightness during the process. The complete release of ACV yielded a hollow PGEDMC/PSS multilayered network with favorable integrity and nano-thickness by TEM and SEM. The potential targetability of the system was proved in vitro by PNA lectin recognition. Lectin hardly adsorbed on the film where the outmost layer was a polyanion or a polycation without galactose component. Whilst the galactose-containing layer (PGEDMC) was the outmost layer, a significant lectin combination was observed. This technique could provide a promising way to encapsulate and deliver various target substances in biological and pharmaceutical applications.     

Supported liquid membranes modification with sulphonated poly(ether ether ketone): Permeability,selectivity and stability

The development of a new type of composite membrane consisting of a microfiltration support membrane, an immobilised liquid membrane phase and a hydrophilic, charged polymer layer and its function as a supported liquid membrane (SLM) for copper selective transport are described. The ion-exchange layers function as stabilisation layers to improve the membrane lifetime and consist of sulphonated poly(ether ether ketone) (SPEEK). This polymer shows a high permeability for copper ions due to the presence of fixed negative charges and to its swelling capacity in an aqueous phase.A method was developed to prepare composite membranes composed of the support membranes Celgard with one stabilisation layer on either the feed or strip side of the membrane or on both sides. Good adhesion of homogeneous, negatively charged, hydrophilic SPEEK layers to the hydrophobic macroporous support membranes could only be established when the support membranes were first hydrophilised with a concentrated sulphuric acid solution containing 5 wt% free SO₃.The lifetime of the SLMs is significantly improved when one stabilisation layer is applied at the strip side or two layers at both sides of the SLM. A second advantage of this composite SLM is the increase in copper flux caused by a decrease in thickness of liquid membrane phase. However, when SPEEK penetrates entirely through some pores of the support membrane, ions diffuse non-specifically through the SPEEK matrix resulting in an undesired selectivity loss. This phenomenon occurs only when thin Celgard membranes are used as support membranes.     

Monte Carlo modeling of ion adsorption at the energetically heterogeneous metal oxide/electrolyte interface: Micro- and macroscopic correlations between adsorption energies

Grand canonical Monte Carlo simulations are carried out for the basic Stern model of the electrical double layer formed at the energetically heterogeneous metal oxide/electrolyte interface. The effect of the global (macroscopic) and local (microscopic) adsorption energies correlations as well as the influence of the model parameter on the surface charge density curves were investigated. The linear dependence of point of zero charge (PZC) as a function of H+ ion adsorption energy proves that the acidic/basic properties of the system are mainly governed by proton uptake/release. Two kinds of systems were taken into account: one neglecting lateral interactions and the other one including them. The effect of electrolyte concentrations as well as the surface heterogeneity on the surface charge density curves were shown too. The presented simulation algorithm allows to model two experimentally observed instances of the metal oxide/electrolyte interface: one possessing a common intersection point (CIP) at pH = PZC and the other one with CIP not equal PZC.     

Effect of separating layer in pervaporation composite membrane for MTBE/MeOH separation

The composite membranes with polyvinylalcohol (PVA) as separating layer material and polyacrylonitrile (PAN) or cellulose acetate (CA) as supporting layer material were prepared for separating methyl tert-butyl ether (MTBE)/MeOH mixture by pervaporation (PV). The results showed that PV performance of the composite membrane with PVA membrane as separating layer was superior to that with CA membrane as separating layer, and the PV performance of PVA/CA composite membrane with CA membrane as supporting layer was better. The parameters to prepare the composite membrane remarkably affected PV performance of the composite membrane. The permeate flux of both composite membranes of PVA/PAN and PVA/CA was over 400 g/m² h, and the concentration of MeOH in the permeate reached over 99.9 wt.% for separating MTBE/MeOH mixture.