Preparation and Properties of Gelatin-Chitosan/Montmorillonite Drug-loaded Microspheres

A kind of slow release drug-loaded microspheres were prepared with gelatin, chitosan and montmorillonite（MMT） by an emulsification/chemical cross-linking method using glutaraldehyde as cross-linking agent and acyclovir as model drug. The microspheres were characterized by X-ray diffraction （XRD）, Fourier transform infrared （FT-IR） and scanning electron microscopy （SEM）, respectively. The morphology, drug content, encapsulation efficiency and drug-release behavior were investigated with different MMT contents. The experimental results indicated that intercalated microspheres could be prepared, the morphology of microspheres was markedly affected by MMT. The glomeration performance of uncross-linked microspheres was improved because of the physical cross-linking of MMT. Drug content and encapsulation efficiency were decreased when increased the content of MMT, but burst release and the drug release were significantly decreased with the addition of MMT. Effective physical cross-linking could be formed when added MMT, and MMT could reduce the content of toxic chemical cross-linking agents.

Synthesis of Novel Chitosan Microspheres Grafted with β-Cyclodextrins and Their Adsorption for Iodine for Antibacterial Activities

The novel chitosan microspheres grafted with beta-cyclodextrins (CMGC) wereprepared by means of the reaction of chitosan microspheres and mono-(6-p-tosyl)- beta-cyclodextrins(beta-CD-OTs-6). beta-CD-OTs-6 were gained by the reaction of p-toluenesul-fonyl chloride (TsCl) andbeta-cyclodextrins (beta-CDs). Their structures were proved by Fourier transform infrared spectralanalysis (FT-IR), X ray powder diffraction analysis, and ^(13)C NMR; the configuration of CMGC wascharacterized by scanning electron micrograph (SEM) and transmittance electron micrograph (TEM). Theinclusion complex of CMGC with iodine was prepared and its inclusion ability was studied. Theexperimental results showed that some iodine was included with CMGC and formed a stable inclusion.The stable complex of CMGC and iodine (CMGC-1) shows good antibacterial effect.

Chitosan and β-cyclodextrin Microspheres as Pulmonary Sustained Delivery Systems

Chitosan and β-cyclodextrin were used to prepare microspheres with theophylline for pulmonary delivery by spray drying method. The characteristics, mucociliotoxicity, permeation rate and drug release were studied. The drug entrapments of microspheres Ⅰ, Ⅱ and Ⅲ were from 35.70% to 21.09% and 13.33%, while yields and encapsulation efficiencies were higher than 45% and about 90% respectively. The microspheres possessed low tap densities （0.34-0.48 g/cm^3）, appropriate diameters （3.35-3.94 μm） and theoretical aerodynamics diameters （2.20-3.04 μm）. SEM images showed the microspheres were spherical with smooth or wrinkled surface surfaces. FT-IR demonstrated theophylline had formed hydrogen bonds with chitosan and fl-cyclodextrin. The microspheres could effectively reduce the ciliotoxicity and easy to penetrate the memberine. The in vitro release of the microspheres was related to the ratio of drug/polymer and microspheres Ⅱ had a prolong release, providing the release of 72.00% in 12 h. The results suggestes that chitosan/β-cyclodextrin microspheres Ⅱ are a promising carrier as sustained release for pulmonary delivery.

Preparation and in vitro Release Performance of Sustained-release Captopril/Chitosan-gelatin Net-polymer Microspheres

The captopril/Chitosan-gelatin net-polymer microspheres(CTP/CGNPMs) were prepared using Chitosan(CTS) and gelatin(GT) by the methods of emulsification,cross-linked reagent alone or in combination and microcrystalline cellulose(MCC) added in the process of preparation of microspheres,which aimed to eliminate dose dumping and burst phenomenon of microspheres for the improvement of the therapeutic efficiency and the decrease of the side effects of captopril(CTP). The results indicated that CTP/CGNPMs had a spherical shape,smooth surface and integral structure inside but no adhesive phenomena in the preparation. The size distribution ranged from 220 μm to 280 μm. The CTP release test in vitro demonstrated that CTP/CGNPMs played the role of retarding the release of CTP compared with ordinary CTP tablets. The release behaviors of CGNPMS were influenced by preparation conditions such as experimental material ratio(EMR) and composition of cross linking reagents. Among these factors,the EMR(1/4),CLR(FA+SPP) and 0.75% microcrystalline cellulose(MCC) added to the microspheres constituted the optimal scheme for the preparation of CTP/CGNPMs. The ER,DL and SR of CTP/CGNPMs prepared according to the optimal scheme were 46.23±4.51%,9.95±0.77% and 261±42%,respectively. The CTP/CGNPMs had the good characteristics of sustained release of drug and the process of emulsification and cross-linking were simple and stable. The CGNPMs are likely to be an ideal sustained release formulation for water-soluble drugs.

Preparation and Characterization in vitro of Sustained-release Captopril/ Chitosan-gelatin Net-polymer Microspheres(Cap/CGNPMs)

The captopril/ Chitosan-gelatin net-polymer microspheres （ Gap/ CGNPMs ） were prepared using Chitosan （ CS ） and gelatin （ Gel ） by the methods of emulsification. A cross linked reagent alone or in combination with microcrystalline cellulose （ MCC ） was added in the process of preparation of microspheres to eliminate dose dumping and burst phenomenon of microspheres for the improvemeat of the therapeutic efficiency and the decrease of the side effects of captopril （ Cap ）. The results indicate that Cap/ CGNPMs have a spherical shape , smooth surface roorphology and integral inside structure and no adhesive phenomena and good roobility , and the size distribution is mairdy from 220 to 280 μm. Researches on the Cap release test in vitro demonstrate that Cap/ CGNPMs are of the role of retarding release of Cap compared with Cap ordinary tablets （COT）, embedding ratio （ER） , drug loading （ DL ）, and swelling ratio （ SR ）, and release behaviors of CGNPMS are influenced by process conditions of preparation such as experimental material ratio （EMR） , composition of cross linking reagents. Among these factors , the EMR（1/4）, CLR （ FOR ＋ TPP） and 0.75% microcrystulline cellulose （MCC） added to the microspheres are the optimal scheme to the preparation of Cap/CGNPMs. The Cap/CGNPMs have a good characteristic of sustained release of drug, and the process of emulsifieation and crossinking process is simple and stable. The CGNPMs is probable to be one of an ideal sustained release system for water-soluble drugs.

Preparation, Characterization and Drug-Release Behaviors of Crosslinked Chitosan/Attapulgite Hybrid Microspheres by a Facile Spray-Drying Technique

A series of chitosan/attapulgite (CTS/APT) hybrid microspheres were prepared by a facile spray-drying technique. The developed hybrid microspheres were characterized by Fourier transform infrared spectra (FTIR), X-ray powder diffraction (XRD), scanning electron microscopy (SEM) and the zeta potential. The encapsulation efficiency and in vitro controlled release properties of the microspheres for drug were evaluated using diclofenac sodium (DS) as a model drug. Results indicated that the introduction of APT into crosslinked CTS microspheres can achieve narrow size distribution and make them more uniform. The isoelectric point of the microspheres increased from 8.14 to 9.18 with increasing the content of APT to 10 wt.%. DS loaded in hybrid microspheres is hardly released in simulated gastric fluid, but quickly released in simulated intestinal fluid. The electrostatic interaction between hybrid microspheres and DS can improve the encapsulation efficiency and controlled release behavior of CTS/APT microspheres, and the release mechanism fits Fickian diffusion.

Optimization of Preparation of Oregano Oil Microspheres by Box-Behnken Response Surface Methodology

[Objectives]To optimize the formulation and preparation of oregano oil microspheres by Box-Behnken response surface methodology.[Methods]Chitosan was used as the carrier material to prepare oregano oil microspheres by emulsion crosslinking method.The encapsulation efficiency,drug loading and ID 50 were used as the evaluation indicators,and the comprehensive score(OD)obtained by"coefficient of variation-AHP comprehensive weighting method"was used as the final evaluation indicator.The formulation design and preparation process were optimized by single factor experiment and Box-Behnken response surface methodology,and the optimal process parameters were determined.[Results]The optimal formulation and preparation process parameters of oregano oil microspheres were as follows:the ratio of oregano oil to chitosan was 2∶1,the emulsifying speed of double emulsion was 200 r/min,the amount of emulsifier in the colostrum was 4%,and the volume of curing agent was 1.0 mL.The average encapsulation efficiency was 45.33%±1.32%,the average drug loading was 30.59%±2.45%,and the median diameter(ID 50)was 52.596μm±0.023%.[Conclusions]The encapsulation efficiency,drug loading and ID 50 of oregano oil chitosan microspheres prepared by emulsion crosslinking method met the requirements.The drug-loaded microsphere not only can be used as a preparation finished product for direct application,but also be used as a product intermediate to lay a foundation for the research and development of subsequent dosage forms.

Fabrication of chitosan microspheres for efficient adsorption of methyl orange

In this article, morphology, structure and size controllable chitosan microspheres with high mechanical strength were synthesized by microfluidic technology combining chemical crosslinking and used as an adsorbent for methyl orange. The synthesized adsorbents were characterized using scanning electron microscopy(SEM),Fourier transform infrared spectroscopy(FTIR), and an Energy Dispersive Spectrometer(EDS). The effect of pH revealed that the adsorption process depended on pH and the pH variation of methyl orange solution after adsorption indicated that adsorption capacity was affected through the associated role of chitosan nature and pH variation. Experimental results suggested that the as-prepared chitosan microspheres were controlled within a narrow size distribution(coefficients of variation is 1.81%), whose adsorption capacity reached to 207 mg·g^(-1) and mechanical strength was suitable to resist forces. In addition, the adsorption isotherm was well fitted with the Langmuir model, and the adsorption kinetic was best described by the pseudo-second-order kinetic model.The high performance microfluidic-synthesized chitosan microspheres have promising potentials in the applications of removing dyes from wastewater.

Relationship between breakthrough curve and adsorption isotherm of Ca(Ⅱ)imprinted chitosan microspheres for metal adsorption

In this work, an equilibrium-dispersion model was successfully established to describe the breakthrough performance of Ca（Ⅱ） imprinted chitosan （Ca（Ⅱ）-CS） microspheres packed column for metal adsorption, and the assumptions of Langmuir isotherms and axial dispersion controlled mass transfer process were confirmed. The axial dispersion coefficient in Ca（Ⅱ）-CS microspheres packed column was found to be almost proportional to the linear velocity and fit for prediction through single breakthrough test. Sensitivity analysis for breakthrough curve indicated the axial dispersion coefficient as well as Langmuir coefficient was sensitive variable for deep removal requirement. The retrieval of the adsorption isotherms of Ca（Ⅱ）-CS microspheres from breakthrough curve was fulfilled by modelling calibration. A strategy based on the correlation between adsorption isotherms and breakthrough performance was further proposed to simplify the column adsorption design using absorbents with small/uniform size and fast adsorption kinetics like Ca（Ⅱ）-CS microspheres to cut down the gap between lab and industry.

Preparation of gastro-resistant pellets containing chitosan microspheres for improvement of oral didanosine bioavailability

The purpose of this work was to introduce a new concept of coated pellets containing chitosan microspheres loaded with didadosine for oral administration,aiming at reducing the frequency of administration and improving the bioavailability by a suitable release profile.Chitosan microspheres were produced under fiuidized bed,followed by extrusion and spheronization to obtain pellets with a mean diameter of about 1 mm.The pellets were then coated with Kollidon VA64 and Kollicoat MAE100P in water dispersion to depict a sustained release profile.Conventional hard gelatine capsules were loaded with these pellets and tested in vitro for their release profile of didadosine.Dissolution testing confirmed that chitosan microsphere pellets provides appropriate sustained release up to 2 h behavior for didanosine.

Elaboration of Materials with Functionality Gradients by Assembly of Chitosan-Collagen Microspheres Produced by Microfluidics

Biopolymers extracted from renewable resources like chitosan and collagen exhibit interesting properties for the elaboration of materials designed for tissue engineering applications,among which are their hydrophilicity,biocompatibility and biodegradability.In many cases,functional recovery of an injured tissue or organ requires oriented cell outgrowth,which is particularly critical for nerve regeneration.Therefore,there is a growing interest for the elaboration of materials exhibiting functionalization gradients able to guide cells.Here,we explore an original way of elaborating such gradients by assembling particles from a library of functionalized microspheres.We propose a simple process to prepare chitosan-collagen hybrid microspheres by micro-and milli-fluidics,with adaptable dimensions and narrow size distributions.The adhesion and survival rate of PC12 cells on hybrid microspheres were compared to those on pure chitosan ones.Finally,functionalized microspheres were assembled into membranes exhibiting a functionalization gradient.

Preparation of biocompatible magnetic microspheres with chitosan

Microsphere is a term used for small spherical particles, with diameters in the micrometer range (typically 1μm to 1000μm (1mm)). Microspheres are sometimes referred to as microparticles. Microspheres can be manufactured from various natural and synthetic materials. The present work we prepared chitosan magnetic microspheres (CMMS) with simple crosslinking method. The obtained CMMS were in size range of 1000-2600 nm with average particle size of 1800nm. All the essential characterizations of prepared CMMS were done and the results were in a good agreement with other magnetic microspheres prepared with different method. To test the biocompatibility of CMMS with blood, the effect of them on erythrocytes aggregation and blood hemolysis were studied. Our results showed that CMMS work as good compatible materials with blood.

Effects of theophylline/chitosan/β-cyclodextrin microspheres for oral drug delivery on an asthmatic rat model

Objective:This study aimed to investigate the effects of TH/CTS/β-CD microspheres by oral administration on ovalbumin allergic asthma of a rat model.Methods:Spray drying method was applied for preparing the TH/CTS/β-CD microspheres,which were used in treatment of asthmatic rats.At a predetermined time,the levels of eosinophil(Eos),protein,lactate dehydrogenase(LDH),aspartate transaminase(AST),glutamic pyruvic transaminase(GPT),and creatinine(Cr)were ascertained by automatic hematology and biochemical analyzers.Lung tissue histology was performed by hematoxylin-eosin staining.Results:No significant differences were found about the contents of Eos in the blood,and the contents of Eos,protein and LDH in the bronchoalveolar lavage fluid between the microsphere-treated and dexamethasone-treated groups,but the levels were lower in both treated groups than in the model group.In the microsphere-treated group,the levels of Cr,AST,and GPT in the serum of rats showed no significant differences compared with the normal group.Based on lung histopathological findings,the microspheres attenuated inflammatory cell infiltration and mucus hypersecretion compared with the model group.Conclusion:This study demonstrated that TH/CTS/β-CD microspheres exerted an anti-inflammatory effect and could serve as a novel promising drug delivery system for asthma treatment.

Preparation of Chitosan-based Microspheres for Rapid Hemostasis

Rapid control of heavy hemorrhaging is critical to save the life of injured individuals.Herein,we developed a novel hemostat employing chitosan-based microspheres,which was prepared by sequential microemulsion of chitosan solution,sol-gel phase transition,and surface modification by 3,4-dihydroxyhydrocinnamic acid(HCA).HCA-modified chitosan microspheres(CSMS-HCA)displayed a porous structure,with a high specific surface area(~211.3 m^(2)/g),accelerating their rapid absorption of blood and concentrating red cells and platelets.The CSMS-HCA exhibited much better in vitro and in vivo hemostatic efficacy than porous chitosan microspheres did.Such a rapid hemostat in the form of microspheres is highly effective in treating deep and irregular wounds,owing to easy accessibility to injured sites.

Hydrogen Peroxide Sensor Based on Horseradish Peroxidase Combined with CaCO_3 Microspheres and Gold Nanoparticles

Direct electrochemistry and electrocatalysis of horseradish peroxidase（HRP） were achieved by entrapping the enzyme between CaCO3 microspheres and gold nanoparticles through forming sandwich configuration （CaCO3-HRP-AuNPs）. Polyanion, poly（styrene sulfonate）（PSS）, was hybrid with CaCO3 microspheres to increase the surface negative charges for binding with HRP through electrostatic interaction. After the bioconjugate CaCO3 PSS-HRP was entrapped in chitosan based sol-gel（CS-GPTMS） film, HRP was encapsulated by in situ formation of an outer layer of AuNPs through electrochemical reduction of HAuCl4. The composite film containing AuNPs, CaCO3-PSS-HRP bioconjugates and CS-GPTMS can provide favorable microenvironment for HRP to perform direct electron transfer at glassy carbon electrode（GCE）. HRP retained its bioelectrocatalytic activity and lead to sensitive and fast amperometric response for the determination of H2O2. H2O2 could be detected in a very wide linear range from 5.0×10-6 mol/L to 7.1×10-2 mol/L. The sandwich configuration of CaCO3-biomolecules-AuNPs could serve as a versatile platform for enzyme immobilization and biosensing.

A partition-type tubular scaffold loaded with PDGF-releasing microspheres for spinal cord repair facilitates the directional migration and growth of cells

The best tissue-engineered spinal cord grafts not only match the structural characteristics of the spinal cord but also allow the seed cells to grow and function in situ.Platelet-derived growth factor（PDGF） has been shown to promote the migration of bone marrow stromal cells;however,cytokines need to be released at a steady rate to maintain a stable concentration in vivo.Therefore,new methods are needed to maintain an optimal concentration of cytokines over an extended period of time to effectively promote seed cell localization,proliferation and differentiation.In the present study,a partition-type tubular scaffold matching the anatomical features of the thoracic 8–10 spinal cord of the rat was fabricated using chitosan and then subsequently loaded with chitosan-encapsulated PDGF-BB microspheres（PDGF-MSs）.The PDGF-MS-containing scaffold was then examined in vitro for sustained-release capacity,biocompatibility,and its effect on neural progenitor cells differentiated in vitro from multilineage-differentiating stress-enduring cells（MUSE-NPCs）.We found that pre-freezing for 2 hours at-20°C significantly increased the yield of partition-type tubular scaffolds,and 30 μL of 25% glutaraldehyde ensured optimal crosslinking of PDGF-MSs.The resulting PDGF-MSs cumulatively released 52% of the PDGF-BB at 4 weeks in vitro without burst release.The PDGF-MS-containing tubular scaffold showed suitable biocompatibility towards MUSE-NPCs and could promote the directional migration and growth of these cells.These findings indicate that the combination of a partition-type tubular scaffold,PDGF-MSs and MUSENPCs may be a promising model for the fabrication of tissue-engineered spinal cord grafts.

Preparation and Self-assembly of Chitosan/Carbon Microsphere Composite

Carbon-based films were synthesized by self-assembly of chitosan-encapsulated carbon microsphere （CMS@CS） composite. First, carbon microspheres （CMSs） prepared by chemical vapor deposition were modified by HNO3 and H2O2. Second, oxidized CMSs were modified by chitosan （CS）. Finally, CMS@CS was self-assembled by vertical deposition, in which suspension concentration and deposition temperature on the quality of self-assembling film were investigated. Field emission scanning electron microscopy, atomic force microscopy, X-ray diffraction, thermogravimetry, and Fourier transformation infrared spectrometry were employed to characterize the morphology and structure of the samples. The results show that CMSs modified by CS had uniform particle size and good dispersion, CMS@CS was self-assembled into a dense film, the film thickened with increasing suspension concentration at fixed temperature, and more ordered film was obtained at 1 wt% of suspension concentration and 50 ℃. The ultraviolet-visible absorption spectra show that the absorbance of CMS@CS film grew steadily with increasing suspension concentration and that the CMSs with oxygen-containing groups have a good assembling performance to form composite films with CS.

Preparation and Characterization of Chitosan Microsphere Loading Bovine Serum Albumin

To optimize the preparation process of chitosan microspheres and study its loading capacity, chitosan microsphere was prepared by crosslinking with glutaraldehyde, and bovine serum albumin （BSA） was absorbed onto chitosan microsphere. Scanning electron microscope （SEM）, Fourier transform infrared spectroscopy （FITR）, TA instruments and zeta potentiometer analyzer were used to characterize the parameters with respect to size, thermal characters, morphology, and zeta potential of the microspheres. The loading capability and in vitro release tests were carried out. The results showed that chitosan microsphere with particle size less than 10 μm and positively charged （＋25.97±0.56 mV） can be obtained under the aldehyde group to amino group ratio at 1：1. A loading capacity of BSA at 28.63±0.15 g/100 g with corresponding loading efficiency at 72.01±1.44% was obtained for chitosan microsphere. In vitro test revealed a burst release followed by sustained-release profile.

Comparison of Dye Adsorption of Three Forms of Chitosan

The purpose of this project is to explore the adsorption rates of different dye methods (direct, reactive, acidic, disperse, azo dyes) in three shapes of chitosan materials (film, microsphere, and scaffold) which were formed by 88% deacetylation degree of chitosan. Results of this research suggest that the samples with larger specific surface areas tend to have shorter adsorption times. Among the three samples, the chitosan scaffold reached the adsorptive saturation on the third day, showing the shortest adsorption time of the direct, reactive, acidic, dispersive and azo dyes, whereas the chitosan film reached the adsorptive saturation on the eighth day, giving it the longest adsorption time of the dyes.