OBJECTIVETo prepare a drug-loading film using chitosan and carboxymethyl chitosan as the carrier materials for delivering matrine to oral ulcers.

METHODSMatrine-loading films using chitosan or carboxymethyl chitosan as the carrier materials were prepared by solution casting method and orthogonal experiment at room temperature. The mechanical properties, surface morphology and drug-loading capacity of the drug-loading film were characterized using tensile test, scanning electron microscopy (SEM), swelling test and in vitro drug release test.

RESULTSWhen the molecular weight of chitosan was 650 000 and the mass ratio of chitosan/glycerol was 1:1.4, the prepared film had the maximum mechanical strength and tensile modulus reaching 0.7875 MPa. SEM observation showed that matrine aggregated at the bottom of the drug-loading film with an asymmetrical distribution. The in vitro drug release test showed that the film had a high drug-loading capacity and a sustained drug release property. The duration of drug release from the drug-loading film was prolonged as the molecular weight of chitosan increased, reaching 23 h when the molecular weight of chitosan was 650 000. The duration of drug release was further increased to 108 h when the bottom of the drug-loading film was coated with a layer of 1% carboxymethyl chitosan.

CONCLUSIONThe matrix materials of the drug-loading film are natural, green, nontoxic and biodegradable, and the preparation of the film is simple without using large quantities of organic solvents. The novel drug-loading film can obviously prolong the duration of drugs release for better local drug delivery to oral ulcers in a sustained manner.

Alkaloids ; chemistry ; Chitosan ; analogs & derivatives ; chemistry ; Delayed-Action Preparations ; Drug Delivery Systems ; Drug Liberation ; Glycerol ; chemistry ; Microscopy, Electron, Scanning ; Quinolizines ; chemistry

In the present study, a risperidone loaded microsphere/sucrose acetate isobutyrate (SAIB) in situ forming complex depot was designed to reduce the burst release of SAIB in situ forming depot and to continuously release risperidone for a long-term period without lagime. The model drug risperidone (Ris) was first encapsulated into microspheres and then the Ris-microspheres were embedded into SAIB depot to reduce the amount of dissolved drug in the depot. The effects of different types of microsphere matrix, including chitosan and poly(lactide-coglycolide) (PLGA), matrix/Ris ratios in microspheres and morphology of microspheres on the drug release behavior of complex depot were investigated. In comparison with the Ris-loaded SAIB depot (Ris-SAIB), the complex depot containing chitosan microspheres (in which chitosan/Ris = 1 : 1, w/w) (Ris-Cm-SAIB) decreased the burst release from 12.16% to 5.80%. However, increased drug release rate after 4 days was observed in Ris-Cm-SAIB, which was caused by the high penetration of the medium to Ris-Cm-SAIB due to the hydrophilie of chitosan. By encapsulation of risperidone in PLGA microspheres, most drugs can be prevented from dissolving in the depot and meanwhile the hydrophobic PLGA can reduce the media penetration effect on the depot. The complex depot containing PLGA microspheres (in which PLGA/ drug=4 : 2, w/w) (Ris-Pm-SAIB) showed a significant effectiveness on reducing the burst release both in vitro and in vivo whereby only 0.64% drug was released on the first day in vitro and a low AUC0-4d value [(105.2± 24.4) ng.mL-1.d] was detected over the first 4 days in vivo. In addition, drug release from Ris-Pm-SAIB can be modified by varying the morphology of microspheres. The porous PLGA microspheres could be prepared by adding medium chain triglyceride (MCT) in the organic phase which served as pore agents during the preparation of PLGA microspheres. The complex depot containing porous PLGA microspheres (which were prepared by co-encapsulation of 20% MCT) (Ris-PPm-SAIB) exhibited a slightly increased AUC0-4d of (194.6±15.8) ng.mL-1d and high plasma concentration levels from 4 to 78 days [Cs(4-78d)=(7.8±1.2) ng.mL-1]. The plasma concentration on 78 day C78d was (9.0 2.5) ng.mL-1 which was higher than that of Ris-Pm-SAIB [C78d= (1.6 ± 0.6) ng.mL-1]. In comparison with Ris-Pm-SAIB, the AUC4-78d of Ris-PPm-SAIB increased from (379.0±114.3) ng.mL-1.d to (465.0 ±149.2) ng.mL-1.d, indicating sufficient drug release from the Ris-PPm-SAIB. These results demonstrate that the risperidone loaded porous PLGA microsphere/SAIB in situ forming complex depot could not only efficiently reduce the burst release of SAIB depot both in vitro and in vivo, but also release the drug sufficiently in vivo, and be capable to continuously release the drug for 78 days.
Chitosan ; Drug Carriers ; Lactic Acid ; Microspheres ; Polyglycolic Acid ; Risperidone ; chemistry ; Sucrose ; analogs & derivatives ; Technology, Pharmaceutical

The purpose of this study is to investigate the penetration effects and mechanism of N-arginine chitosan (ACS). This novel transdermal enhancer with a mimetic structure of cell-penetration peptides was synthesized by introducing hydrophilic arginine groups to the amino-group on chitosan's side chain. The structure of ACS was confirmed by FT-IR, 1H NMR and element analysis. In addition, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) was used to study the protein conformation and the water content of stratum corneum, and the result suggested that ACS can change the orderly arrangement of the molecules in the stratum corneum, making the stack structure of keratin become loose. And ACS can increase the water content of the stratum corneurn. Inverted fluorescence microscope and flow cytometry were used to examine penetration effect of ACS on Hacat cell. The result confirmed that the uptake of ACS was enhanced with increased substitution degree of arginine by 4-8 folds compared to chitosan. In vitro penetration studies on three electrical types of drugs were carried out using three model drugs of negatively charged aspirin, positively charged terazosin and neutral drug isosorbide mononitrate by the method of Franz diffusion cells. The results showed that ACS has obviously penetration of the negatively charged drug aspirin, and certain penetration of neutral drug issorbide mononitrate, but inhibition of positively charged terazosin. In vivo imaging technology research results show that the ACS can significantly enhance the fluorescence intensity of morin, which is the auto-fluorescence anionic drug. These obtained results suggested that ACS, as a promising transdermal enhancer, can change the structure of the keratinocytes and analog penetrating peptides promote absorption, but have certain selectivity for the drug.
Administration, Cutaneous ; Animals ; Arginine ; chemical synthesis ; chemistry ; pharmacology ; Aspirin ; administration & dosage ; pharmacokinetics ; Cell Line ; Cell Survival ; drug effects ; Cell-Penetrating Peptides ; chemical synthesis ; chemistry ; pharmacology ; Chitosan ; chemical synthesis ; chemistry ; pharmacology ; Drug Carriers ; Humans ; Isosorbide Dinitrate ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Keratinocytes ; cytology ; Male ; Mice ; Prazosin ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Skin Absorption ; drug effects

The concentrations of heavy metals in the extracting solutions of traditional Chinese medicine are usually very low. Furthermore, a vast number of organic components contained in the extracting solutions would be able to coordinate with heavy metals, which might lead to great difficulty in high efficient removal of them from the extracting solutions. This paper was focused on the removal of heavy metals of low concentrations from the extracting solution of Angelica sinensis by applying an EDTA-modified chitosan magnetic adsorbent (EDTA-modified chitosan/SiO2/Fe3O4, abbreviated as EDCMS). The results showed that EDCMS exhibited high efficiency for the removal of heavy metals, such as Cu, Cd and Pb, e.g. the removal percentage of Cd and Pb reached 90% and 94.7%, respectively. Besides, some amounts of other heavy metals like Zn and Mn were also removed by EDCMS. In addition, the total solid contents, the amount of ferulic acid and the HPLC fingerprints of the extracting solution were not changed significantly during the heavy metal removal process. These results indicate that EDCMS may act as an applicable and efficient candidate for the removal of heavy metals from the extracting solution of A. sinensis.
Adsorption ; Angelica sinensis ; chemistry ; Chitosan ; chemistry ; Drug Contamination ; prevention & control ; Edetic Acid ; analogs & derivatives ; chemistry ; Magnetics ; methods ; Metals, Heavy ; chemistry ; isolation & purification

OBJECTIVETo investigate the effects of three kinds of artificial dermal scaffolds on vascularization and scar formation of wounds in pigs with full-thickness burn.

METHODSEighteen Bama miniature pigs were divided into chitosan scaffold (CS) group, sulfonated carboxymethyl chitosan scaffold (SCCS) group, and acellular dermal matrix (ADM) scaffold group according to the random number table, with 6 pigs in each group. Every pig in all groups was inflicted with 4 or 8 full-thickness scald wounds on the back (totally 96 wounds). Forty-eight hours after injury, eschars of all wounds were excised. Twenty-four wounds in CS group were transplanted with double-layer artificial dermis of collagen-chitosan and silicone rubber, those in SCCS group with double-layer artificial dermis of collagen-sulfonated carboxymethyl chitosan and silicone rubber, and those in ADM scaffold group with ADM. The rest 24 wounds in the three groups were dressed with vaseline gauze as control group. After 2 weeks of treatment, all wounds of every group were covered with skin. In post treatment (scaffold transplantation or gauze covering) week (PTW) 1, 2, 3, and 4, gross condition of wound was observed, and specimens from central parts of wounds were harvested for observation and assessment of vessels or cells with positive expression of CD31, α smooth muscle actin (α-SMA), TGF-β(1) and TGF-β(3) with SP staining. Data were processed with one-way analysis of variance and LSD test.

RESULTS(1) Degree of vascularization in SCCS group was better than that in the other three groups. (2) The number of vessels with positive expression of CD31 in CS, SCCS, ADM scaffold, and control groups increased gradually from PTW 1 to PTW 3, and decreased in PTW 4. There were statistical differences among 4 groups from PTW 1 to PTW 4 (with F value respectively 24.005, 38.822, 25.274, 3.856, P < 0.05 or P < 0.01). The numbers of vessels that expressed CD31 in SCCS group from PTW 1 to PTW 3 were more than those in the other three groups (with P values all below 0.05). (3) The numbers of vessels that expressed α-SMA in CS, SCCS, and ADM scaffold groups from PTW 1 to PTW 3 showed the similar trend of change to those of vessels that expressed CD31, which increased gradually in control group from PTW 1 to PTW 4. There were obvious differences among 4 groups from PTW 1 to PTW 4 (with F value respectively 22.637, 28.087, 62.651, 18.055, P values all below 0.01). The number of vessels that expressed α-SMA in SCCS group from PTW 1 to PTW 4 was more than that in the other three groups (with P values all below 0.05). (4) From PTW 1 to PTW 4, the number of cells with expression of TGF-β(1) in CS group was respectively (127 ± 8), (167 ± 19), (170 ± 18), (144 ± 10) per 400 times visual field, that in SCCS group was respectively (171 ± 17), (207 ± 25), (130 ± 30), (69 ± 16) per 400 times visual field, that in ADM scaffold group was respectively (106 ± 8), (159 ± 17), (171 ± 11), (145 ± 11) per 400 times visual field, and that in control group was respectively (100 ± 20), (150 ± 18), (200 ± 14), (172 ± 20) per 400 times visual field. There were statistical differences among 4 groups from PTW 1 to PTW 4 (with F value respectively 29.675, 9.503, 13.107, 54.515, P values all below 0.01). Compared with those in SCCS group, the number of cells that expressed TGF-β(1) in the other three groups was decreased in PTW 1, 2 but increased in PTW 3, 4 (with P values all below 0.05). (5) The number of cells that expressed TGF-β(3) in 4 groups increased gradually from PTW 1 to PTW 3, and decreased or increased continually in PTW 4. There were statistical differences among 4 groups from PTW 1 to PTW 4 (with F value respectively 140.612, 945.850, 714.037, 119.147, P values all below 0.01). The number of cells with positive expression of TGF-β(3) in SCCS group from PTW 1 to PTW 4 was more than that in the other three groups (with P values all below 0.05).

CONCLUSIONSThe collagen-sulfonated carboxymethyl chitosan dermal scaffold can rapidly induce growth and maturation of blood vessels during wound healing after burn. It is beneficial for wound repair at early stage with inhibition of scar proliferation.

Acellular Dermis ; Animals ; Burns ; surgery ; Chitosan ; analogs & derivatives ; Cicatrix ; pathology ; Collagen ; Dermis ; transplantation ; Female ; Neovascularization, Physiologic ; Skin Transplantation ; Skin, Artificial ; Swine ; Tissue Scaffolds ; Wound Healing

The chitosan scaffolds with different deacetylated degree were prepared in this study. The morphology of scaffolds were observed using SEM, and the porosity, the water absorbing swelling ratio and the degradation were examined both in vitro and in vitro. The results showed that the chitosan scaffolds with different deacetylated degree exhibited three-dimensional structure with high porosity. With increasing of deacetylated degree, their porosities were 93.46%, 90.02% and 86.71%, respectively. The swelling ratios of chitosan scaffolds were 820%, 803% and 772%, respectively. At the fourth week, the degradation rates were 30.44%, 22.08% and 17.10% in vitro, respectively; while the corresponding rates were 57.48%, 40.23%, 29.53% in vivo respectively. The degradation rate of chitosan scaffold was negatively correlated to deacetylated degree. Furthermore, it showed that the speed of degradation in vivo was faster than that in vitro. We concluded that controlling the deacetylated degree of chitosan can provide a well-matched degradable scaffold material for the reparation of cartilage defects.
Absorbable Implants ; Acetylation ; Animals ; Biocompatible Materials ; Chitosan ; analogs & derivatives ; chemical synthesis ; chemistry ; Female ; Male ; Materials Testing ; Rats ; Rats, Sprague-Dawley ; Tissue Engineering ; Tissue Scaffolds ; chemistry

A novel chitosan derivant, N-octyl-N-arginine chitosan (OACS) with a mimetic structure of cell-penetrating peptides was synthesized by introducing hydrophilic arginine groups and hydrophobic octyl groups to the amino-group on chitosan's side chain. Structure of the obtained polymer was characterized by FT-IR and 1H NMR. The substitution degree of octyl and arginine groups was calculated through element analysis and spectrophotometric method, separately. The critical micelle concentration of OACS was 0.12 - 0.27 mgmL(-1) tested by fluorescence spectrometry. The solubility test showed OACS could easily dissolve in pH 1 - 12 solutions and self-assemble to form a micelle solution with light blue opalescence. The OACS micelles have a mean size of 158.4 - 224.6 nm, polydisperse index of 0.038 - 0.309 and a zeta potential of +19.16 - +30.80 mV determined by malvern zetasizer. AFM images confirmed free OACS micelle has a regular sphere form with a uniform particle size. MTT test confirmed that OACS was safe in 50 - 1 000 micromol-L(-1). The result of HepG2 cell experiment showed that the cell internalization of OACS micelles enhanced with increased substitution degree of arginine by 40 folds compared to chitosan. Thus, OACS micelles were a promising nano vehicle with permeation enhancement and drug carrier capability.
Arginine ; analogs & derivatives ; chemical synthesis ; chemistry ; metabolism ; Biocompatible Materials ; chemical synthesis ; chemistry ; Cell Survival ; Cell-Penetrating Peptides ; chemical synthesis ; chemistry ; Chitosan ; analogs & derivatives ; chemical synthesis ; chemistry ; Drug Carriers ; Hep G2 Cells ; Humans ; Magnetic Resonance Spectroscopy ; Micelles ; Nanoparticles ; Particle Size ; Polymers ; Solubility ; Spectroscopy, Fourier Transform Infrared

The aim of this study was to develop a sustained release converse thermosensitive hydrogel for intra-articular injection using chitosan-glycerol-borax as matrix, its physical properties and biocompatibility were investigated. Taking gelation time and gelation condition as index, the influence of concentration of chitosan, ratio of chitosan to glycerol, pH on physical properties of hydrogel were investigated. And then the in vitro drug release, rheological properties and biocompatibility were studied. The thermosensitive hydrogel flows easily at room temperature and turns to gelation at body temperature, which can certainly prolong the release of drug and has good biocompatibility.
Analgesics ; administration & dosage ; adverse effects ; chemistry ; Animals ; Chitosan ; administration & dosage ; chemistry ; Delayed-Action Preparations ; Drug Compounding ; Hydrogels ; administration & dosage ; chemistry ; Hydrogen-Ion Concentration ; Inflammation ; chemically induced ; Injections, Intra-Articular ; Knee Joint ; drug effects ; Male ; Materials Testing ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Rheology ; Seeds ; chemistry ; Strychnine ; administration & dosage ; adverse effects ; analogs & derivatives ; chemistry ; Strychnos nux-vomica ; chemistry ; Surface Properties ; Synaptic Membranes ; drug effects ; Temperature

In order to investigate the effects of HA whisker and carboxymethyl chitosan-gelatin(CMC-Gel) on the mechanical properties of porous calcium phosphate cement, a series of alpha-tricalcium phosphate (alpha-TCP), HA whisker and L-sodium glutamate porogen with different mass fractions were mixed, and setting liquid was added to them to prepare alpha-TCP/HA whisker composite porous bone cement. Then, the cement was immersed in a series of CMC-Gel solutions which had different weight ratios of CMC to Gel to prepare alpha-TCP/HA whisker/CMC-Gel composite porous bone cement. The compressive strengths and microstructure of cement were characterized by mechanical testing machine and SEM. The results showed that when the mass fraction of HA whisker is 4%, the compressive strength of alpha-TCP/HA whisker composite porous bone cement reaches 2.57MPa, which is 1.81 times that of alpha-TCP bone cement. When the weight ratio of CMC to Gel is 50:50, the compressive strength of alpha-TCP/HA whisker/CMC-Gel composite porous bone cement is 3. 34MPa, which is 2.35 times that of alpha-TCP bone cement, and the toughness of the composite cement is greatly improved as well.
Biocompatible Materials ; chemistry ; pharmacology ; Bone Cements ; chemical synthesis ; Calcium Phosphates ; chemistry ; Chitosan ; analogs & derivatives ; chemical synthesis ; chemistry ; Compressive Strength ; Gelatin ; chemistry ; Hydroxyapatites ; chemical synthesis ; chemistry ; Porosity

Folic acid-O-carboxymethyl chitosan ultrasmall superparamagnetic iron oxide nanoparticles (FA-OCMCS-USPIO-NPs) are a novel molecular targeting MR contrast agent. This paper reperts the pharmacokinetics and magnetic resonance response characteristics of FA-OCMCS-USPIO-NPs in normal rats and mice, and discussed its distributing regularity in animals, providing basis for tumor targeting imaging. O-phenanthroline method was used to determine iron content in rats' plasma and mice's organs following high and low doses of nanoparticles injected through tail vein, and the blood concentration-time curve was drawn, the calculated t1/2 of two groups were greater than 7 h. The results of tissue distribution showed that only a small part of nanoparticles were swallowed by the liver and spleen, while none in the heart, lung and kidney. At the same times, the phagocytosis of nanoparticles did not change with the dose. The results of MRI showed that renal excretion occurred 4 hours after injection, and signal to noise ratio (SNR) of liver and kidney returned to normal levels 24 hours after injection. There were no nanoparticles in the lungs. So a part of nanoparticles escaped from phagocytosis of liver and spleen, and it owned lower toxicity and longer half-life. indicated its use for tumor-targeting imaging. All of these indicated its use for tumor-targeting imaging.
Animals ; Area Under Curve ; Chitosan ; administration & dosage ; analogs & derivatives ; chemistry ; pharmacokinetics ; Contrast Media ; administration & dosage ; chemistry ; pharmacokinetics ; Dose-Response Relationship, Drug ; Drug Carriers ; Ferric Compounds ; administration & dosage ; chemistry ; pharmacokinetics ; Folic Acid ; administration & dosage ; chemistry ; pharmacokinetics ; Injections, Intravenous ; Magnetic Resonance Imaging ; Magnetite Nanoparticles ; administration & dosage ; chemistry ; Male ; Mice ; Nanoparticles ; Particle Size ; Phagocytosis ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution