Effect of preparation temperature in solvent evaporation process on Eudragit RS microsphere properties

Eudragit RS 100 microspheres containing ketoprofen as a model drug were prepared by the solvent evaporation method using an acetone/liquid paraffin solvent system. The influence of various preparation temperatures: 10, 25, 35, and 40 degrees C, on particle size and morphology, drug content and release kinetics, and drug crystal state was evaluated. With increasing temperature, microsphere average size was found to increase and particle size distribution to widen significantly. At 10 degrees C particles of irregular shape are formed, whereas higher temperatures gradually improve the sphericity of microspheres. As can be seen from SEM photographs, particle surface roughness decreases as preparation temperature increases. It was found that temperature had no effect either on ketoprofen microencapsulation efficiency or on its crystal state, but it does influence emulsion-stabilizer incorporation. Ketoprofen forms solid solution in Eudragit matrix and maintains amorphous state for significant period of time. Drug release rates from microspheres correlated with microspheres' surface roughness and to a lesser extent with particle size.     

Effect of cyclodextrins on physico-chemical and release properties of Eudragit RS 100 microparticles containing glutathione

The objective of this work was to develop a novel microparticulate system based on the mucoadhesive polymer Eudragit-RS 100 and cyclodextrins (CDs), potentially useful for the oral administration of Glutathione (γ–glutamylcysteinylglycine, GSH). For this purpose, an oil-in-oil (O/O) emulsion-solvent evaporation method was used for the preparation of microparticles (MPs) containing GSH alone or together with one of the following CDs: α-, β-, γ-, methyl-β-(Me-β-), hydroxypropyl-β-(HP-β-) or sulfobutylether-β-cyclodextrin (SBE_7m-β-CD). MPs were obtained by emulsifying a mixture of Eudragit RS 100, GSH, CD and magnesium stearate in acetone or acetonitrile with a mixture of liquid paraffin and Span 80. Size, encapsulation efficiency, and drug release of the prepared MPs were evaluated. The results clearly indicated that all the examined properties were dependent on the water-miscible solvents and CD used. In particular, MPs prepared by using acetone or acetonitrile showed different size distributions with mean diameters in the ranges 82–350 and 15–22 μm, respectively. Moreover, encapsulation efficiency values were found to be high in all cases (71–99%) and was significantly affected by the CD type. The GSH release rates were evaluated employing dissolution media with different pH values (1.2, 6.8 and 7.4) and the following rank order was obtained for MPs prepared using acetone: MPs incorporating Me-β-CD > MPs without CD > MPs incorporating the remaining CDs. On the other hand, MPs prepared using acetonitrile gave the highest GSH release rate. Finally, stability of GSH encapsulated in MPs containing HP-β-CD to enzymatic attack by pepsin A, α-chymotrypsin, and γ-glutamyltranspeptidase was also investigated.     

Preparation and properties of chitosan microspheres based on polyglycerol polyricinoleate stabilized emulsions

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The influence of UV irradiation on the properties of chitosan films containing keratin

The mechanical, thermal and surface properties of chitosan and chitosan containing keratin hydrolysates have been studied and the influence of UV irradiation on these properties has been compared. The surface properties of chitosan films containing 5%, 15% and 30% of keratin hydrolysate before and after UV irradiation (λ = 254 nm) were investigated by means of contact angle measurements allowing the calculation of surface free energy. The chemical and structural changes during UV irradiation were studied by UV-vis and FTIR-ATR spectroscopy.The changes in mechanical properties such as breaking strength, percentage elongation and Young’s modulus have been investigated. The results have shown that the mechanical properties of the chitosan/keratin films were greatly affected by UV irradiation, but the level of the changes of these properties was smaller in the blend than in pure chitosan and strongly dependent on the time of irradiation and composition of the samples. The contact angle and the surface free energy were altered by UV irradiation, which indicates photooxidation and an increase of polarity of specimens. The range of these changes point to greater susceptibility of chitosan to photooxidation in the presence of keratin.     

Immune stimulating activity of an atrophic rhinitis vaccine associated to pegylated chitosan microspheres in vitro

It has previously been found that chitosan microspheres are easily aggregated due to their physical and storage instabilities. In this study, to overcome their instability, chitosan was covalently conjugated with poly(ethylene glycol). Pegylated chitosan microspheres were prepared through the ionic gelation process of pegylated chitosan with tripolyphosphate. Bordetella bronchiseptica dermonecrotoxin, major virulence factor of atrophic rhinitis causative agent, was loaded onto pegylated chitosan microspheres for nasal vaccination. Average particle sizes of Bordetella bronchiseptica dermonecrotoxin-loaded pegylated chitosan microspheres were 5.47 µm. Microspheres obtained from pegylated chitosan microspheres were physically more stable than those from chitosan microspheres, and Bordetella bronchiseptica dermonecrotoxin-loaded pegylated chitosan microspheres released more Bordetella bronchiseptica dermonecrotoxin than Bordetella bronchiseptica dermonecrotoxin-loaded chitosan microspheres in vitro. Macrophage RAW264.7 cells stimulated with Bordetella bronchiseptica dermonecrotoxin-loaded pegylated chitosan microspheres gradually secreted tumor necrosis factor α and nitric oxide, suggesting that pegylated chitosan microspheres are very promising vaccine delivery systems. Copyright © 2007 John Wiley & Sons, Ltd.     

Study on colon-specific 5-Fu pH-enzyme Di-dependent chitosan microspheres

Colon-specific drug delivery systems (CDDS) can improve the bioavailability of drug through the oral route. A novel formulation for oral administration using pH-enzyme Di-dependent chitosan mcirospheres (MS) and 5-Fu as a model drug has been investigated for colon-specific drug delivery by the emulsification/chemical cross-linking and coating technique, respectively. The influence of polymer concentration, ratio of drug to polymer, the amount of crosslinking agent and the stirring speed on the encapsulation efficiency, particle size in microspheres were evaluated. The best formulation was optimized by an orthogonal design. Drug release studies under conditions mimicking stomach to colon transit have shown that the drug was protected from being released in the physiological environment of the stomach and small intestine. The plasma concentrations of 5-Fu after oral administration of coated chitosan MS to rats were determined and compared with that of 5-Fu solution. The in vivo pharmacokinetics study of 5-Fu loaded pH-enzyme Di-dependent chitosan MS showed sustained plasma 5-Fu concentration-time profile. The in vitro release correlated well with the pharmacokinetics profile. The results clearly demonstrated that the pH-enzyme Di-dependent chitosan MS is potential system for colon-specific drug delivery of 5-Fu.     

Characterization and release behaviors of porous PCL/Eudragit RS microcapsules containing tulobuterol

In this work, porous poly(ɛ-caprolactone) (PCL)/Eudragit RS 100 (ERS-100) microcapsules containing tulobuterol base as a model drug were prepared by a solvent evaporation method and the effect of the quaternary ammonium groups of ERS-100 on the release behaviors of the microcapsules was investigated. The microcapsules prepared with PCL alone showed a stable and smooth surface, whereas porous microcapsules were formed with the addition of ERS-100. Drug loading and encapsulation efficiency of the microcapsules were slightly decreased with an increase of ERS-100 content, resulting from an increase in the porosity of the microcapsules. In an acidic release medium, PCL microcapsules showed slow drug release, whereas PCL/ERS-100 microcapsules showed a faster release rate with an increasing ERS-100 content. These behaviors are likely due to an increase in the diffusion rate of the drugs stemming from an increased hydration of the microcapsules, which results from the interaction between the carboxyl group of the release medium and the quaternary ammonium group of ERS-100.     

Vitamin A and vitamin E interaction behavior on chitosan microspheres

Chitosan is a biodegradable natural polymer with great potential for pharmaceutical applications due to its biocompatibility, high charge density, and non-toxicity. In this study, chitosan microspheres were successfully prepared by an adapted method of coagulation/dispersion. The degree of deacetylation of chitosan powder was obtained by NMR ¹H and FTIR techniques. Chitosan powder and chitosan microspheres were characterized by BET surface area and scanning electron microscopy (SEM). The interactions among the chitosan microspheres and the vitamins A and E were characterized by FTIR. In order to evaluate the ability of interaction of vitamin A and vitamin E with the chitosan microspheres, the thermodynamic parameters were followed by calorimetric titration. Different experimental approaches were applied, such as adsorption isotherms, kinetics and thermodynamics studies. The obtained results showed that the interactions of chitosan microspheres with the vitamins were spontaneous, enthalpically and entropically favorable, indicating that the chitosan microspheres can be used with success in the controlled release of these vitamins.     

The influence of oxidative degradation on the preparation of chitosan nanoparticles

Chitosan nanoparticles were obtained via ionic crosslinking by using the sulfate ion. Chitosan molecular weight was varied by oxidative degradation of the chitosan β-glycoside bond, the molecular weight being indirectly monitored as the chitosan solution reduced viscosity at a fixed polymer concentration. The dependence between some physical properties of the resultant dispersions (turbidity, viscosity, zeta potential, and sedimentation column profile) and reduced viscosity was established. Atomic force microscopy images have shown the resultant particles formed to be clusters of chitosan nanoparticles with a diameter of ca. 70 nm, the interaction between these particles being characterized by FTIR spectroscopy as the result of sulfate bridging. At the end of the paper, the potential of these dispersions for the incorporation of anionic drugs via adsorption was evaluated using a model compound. The resultant dispersions were capable of adsorbing more than 25% of mass of chitosan, being the partition coefficient higher than 3,500.     

The influence of chondroitin sulfate on composite multilamellar liposomes containing chitosan

A composite multilamellar liposome containing chitosan attached to the inside and outside of the membrane as well as an opposite charged polyelectrolyte, chondroitin, adsorbed at the surface was developed. Not only the chitosan/chondroitin ratio but also the concentration of them were varied. The structure and superficial properties of the liposomes were studied through a combination of light scattering, zeta potential, and small-angle X-rays scattering techniques. While the chitosan/chondroitin ratio affected the superficial charge distributions, the concentration of polyelectrolytes affected the structural properties of the liposomes, as the rigidity of the phospholipid layers. The superficial charge of the resultant composite liposome was influenced by the type and concentration of the polyelectrolyte. Information about the charge density could be obtained by the treatment of zeta potential data, and it was used to estimate the amount of chondroitin adsorbed to the liposome surface. Applying the modified Caillé theory to the X-rays scattering curves, information about the internal structure of the liposomes was accessed. The ability to control the properties of composite multilamellar liposomes is an important issue when they have to be applied as a biomaterial device component.     

磁性壳聚糖微球的制备和应用

磁性壳聚糖微球是通过一定的方法用壳聚糖将磁性材料包埋而形成的磁性微球,其内核为纳米级的磁性金属微粒,外层为壳聚糖.壳聚糖含有大量的氨基和羟基,使其具有特定的理化性质,由此奠定了壳聚糖的许多生物学特性及加工特性的基础.另一方面,其磁性内核使磁性壳聚糖微球具有很好的顺磁性,利用外加磁场可以很方便地进行分离.因此磁性壳聚糖在固定化酶、污水处理、食品工业和生物医药等方面具有广泛的用途,磁性壳聚糖的制备及应用的相关研究也越来越受到重视.本文作者对磁性壳聚糖微球的制备和应用进行评述.     

Controllable preparation of nanoparticle-coated chitosan microspheres in a co-axial microfluidic device

In this work, we describe a novel and simple microfluidic method for fabricating nanoparticle-coated chitosan microspheres. Uniform droplets of aqueous chitosan solution were dispersed into an oil phase containing partially hydrophilic nanoparticles via a co-axial microfluidic device. Recirculating flow in the continuous phase in the area between drops enhanced mixing and allowed the nanoparticles to coat the surface of the droplets as they passed through the channel. The chitosan droplets were then crosslinked with glutaraldehyde and nanoparticle-coated microspheres were obtained. SEM characterization shows that the microspheres are monodispersed with uniform nanoparticle distribution on the surface. The dispersity, size and composition of the microspheres could all easily be controlled by changing the microfluidic flow parameters and three different types of nanoparticles were successfully used to synthesize hybrid microspheres to demonstrate the method's versatility.     

Preparation of magnetic chitosan microspheres and its applications in wastewater treatment

The methods of preparation of magnetic chitosan microspheres have been introduced. In addition, their applications in the wastewater treatment, based on different kinds of wastewater, have been reviewed, and their mechanisms have been discussed. Supported by the Key Natural Science Foundation of China (Grant No. 50633030)     

The influence of chitosan on cyclodextrin complexing and solubilizing abilities towards drugs

The present work was performed to investigate the effect of chitosan, a well known hydrophilic polymer with both enhancer and solubilizing properties, on the solubilizing and complexing abilities of cyclodextrins towards drugs. With this aim, phase-solubility studies were carried out with a series of model drugs, both of acid and basic nature and with different water-solubility and lipophilicity values, in the presence of chitosan and cyclodextrin (ß- or hydroxypropyl-ß-cyclodextrin), both separately (binary systems) and in combination (ternary systems). Unexpectedly, differently from the favorable effect reported in literature for various hydrophilic polymers, the addition of chitosan to the cyclodextrin complexation medium caused a decrease in the cyclodextrin complexing power towards all the examined drugs, independent from their very different physicochemical properties. On the contrary, the influence of the polymer on the cyclodextrin solubilizing efficiency was found to be dependent on the type of drug and both positive, or negative or non-significant effects were observed. The overall results are explained in terms of a common basic mechanism due to the presence of chitosan–cyclodextrin interactions, which hindered the drug–cyclodextrin complex formation, thus causing the binding constant reduction; the simultaneous presence of drug–chitosan and/or chitosan–(drug–cyclodextrin complex) interactions, different from drug to drug, were considered responsible for the distinct (and sometimes opposite) effects observed in the drug solubilizing efficiency of ternary systems.     

Emulsification properties of chitosan

 The chitosans use as an emulsifier in food emulsions was explored. The properties of chitosan (air/solution surface activity, electrical conductivity, HLB) were studied. The obtained emulsions were stable multiple w/o/w emulsions, whose characteristics were explained on the basis of the emulsifier structure and solution properties. The reaction with an anionic surfactant, sodium dodecylsulfate, was also studied, giving a water-insoluble complex at a given surfactant/chitosan ratio. Received: 24 March 1998 Accepted: 13 July 1998     

Colon specific chitosan microspheres for chronotherapy of chronic stable angina

In the present work, chitosan microspheres with a mean diameter between 6.32 μm and 9.44 μm, were produced by emulsion cross-linking of chitosan, and tested for chronotherapy of chronic stable angina. Aiming at developing a suitable colon specific strategy, diltiazem hydrochloride (DTZ) was encapsulated in the microspheres, following Eudragit S-100 coating by solvent evaporation technique, exploiting the advantages of microbiological properties of chitosan and pH dependent solubility of Eudragit S-100. Different microsphere formulations were prepared varying the ratio DTZ:chitosan (1:2 to 1:10), stirring speed (1000-2000 rpm), and the concentration of emulsifier Span 80 (0.5-1.5% (w/v)). The effect of these variables on the particle size and encapsulation parameters (production yield (PY), loading capacity (LC), encapsulation efficiency (EE)) was evaluated to develop an optimized formulation. In vitro release study of non-coated chitosan microspheres in simulated gastrointestinal (GI) fluid exhibited a burst release pattern in the first hour, whereas Eudragit S-100 coating allowed producing systems of controlled release diffusion fitting to the Higuchi model, and thus suitable for colon-specific drug delivery. DSC analysis indicated that DTZ was dispersed within the microspheres matrix. Scanning electron microscopy revealed that the microspheres were spherical and had a smooth surface. Chitosan biodegradability was proven by the enhanced release rate of DTZ in presence of rat caecal contents.     

Fabrication and drug release behavior of ionically cross-linked chitosan microspheres

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In situ biomimetic formation of nano‐hydroxyapatite crystals on chitosan microspheres

Chitosan (CS) is a biocompatible, noncytotoxic biomaterial used before as base material for composites. On the other hand, nano‐hydroxyapatite (nHA) is one of the main components of human bones, highly used for biomedical applications. In this work, CS microspheres were produced under a W/O emulsion system. CS microspheres with calcium ions were then exposed to Na₃PO₄ solution. In situ biomimetic nHA crystals were formed on CS microspheres to generate 15.14 ± 3.15‐μm composite microspheres. The microspheres were subsequently seeded with MG63 osteoblasts to observe their cell responses. All microspheres were characterized via scanning electron microscopy (SEM), phase‐contrast photomicroscopy, and X‐ray diffraction (XRD) analysis. The results showed flake‐like shape and islet‐like growth of nHA depositions presented on the surface of the CS microspheres. In vitro tests indicated that the CS/nHA microparticles were not only biocompatible but also enhanced cell adhesion and elongation due to the in situ biomimetic synthesis method.     

Release characteristics of cisplatin chitosan microspheres and effect of containing chitin

To increase cisplatin (CDDP) content, to suppress burst effect during the initial phase of drug release, and to improve the capacity of the system for sustained release, we prepared various types of CDDP chitosan microspheres incorporating chitin and investigated the content of CDDP and its in vitro release kinetics from these microspheres. The results of this study showed that the CDDP content increased with increasing chitosan concentration and that the incorporation of chitin in the carrier matrix produced a more pronounced increase in drug content. The addition of chitin also led to inhibition of the initial burst effect. The rate of CDDP release reduced with increasing concentration of chitosan: that is, the 50% CDDP release time was about 0.5 h with the microspheres prepared with 1.0% of chitosan and about 4.5 h with those prepared with 5.0% of chitosan, indicating about nine-fold prolongation. The addition of chitin further resulted in retardation of the rate of CDDP release. Meanwhile, our chitosan microspheres were shown to undergo enzymatic degradation by lysozymes.