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

OBJECTIVETo optimize the preparation of genistein chitosan microspheres with central composite design (CCD).

METHODThe chitosan microspheres were prepared by the O/W/O multiple emulsion method. Second-order polynomial and linear equations were fitted to the data, and the resulting equations were used to produce response surface graphs and the best experiment conditions.

RESULTThe theoretical drug content was 13%-15%, the concentration of organic phase was 30%-40% and the concentration of oil phase was 68%-72%.

CONCLUSIONThe best experiment conditions can be obtained by central composite design and response surface methodology. The observed values agree well with model predicted values.

Antineoplastic Agents ; administration & dosage ; Chitin ; analogs & derivatives ; Chitosan ; Delayed-Action Preparations ; Genistein ; administration & dosage ; Mathematics ; Microspheres

OBJECTIVETo construct multifunctonal nano-delivery system crossing the blood brain barrier (BBB).

METHODSThe magnetic nanoparticles were preprared with O-carboxylmethylated chitosan (O-CMC) and conjugated with a peptide sequence from the human immunodeficiency virus 1-tat protein and transferrin (Tf), and anti-tumor drug methotrexate (MTX), and thus constructed a O-CMC magnetic nanoparticles carrier system conjugating with Tat and Tf (O-MNPs-Tat-Tf) that combines multiple functions including crossing BBB, magnetism, receptor-mediated dual targets and anti-tumor capabilities. The appearance, diameter, and magnetism of MTX-O-MNPs-Tat-Tf carrier system were characterized with transmission electronic microscopy, atomic force microscopy and vibrating samples magnetometer. The cytotoxicity of MTX-loaded O-MNPs-Tat-Tf was investigated with C6 glioma cells. The ability of O-MNPs-Tat-Tf crossing BBB was investigated in rats by single photon emission computed tomography.

RESULTSThe mean particle diameter was 75 nm, along with good anti-tumor property. The multi-functioned carrier system successfully crossed the BBB in rat.

CONCLUSIONThe establishment of MTX-O-MNPs-Tat-Tf carrier model implies a promising future for its application in therapy of cerebral diseases.

Blood-Brain Barrier ; drug effects ; metabolism ; Chitosan ; analogs & derivatives ; chemistry ; Drug Carriers ; Drug Delivery Systems ; Humans ; Magnetics ; Nanoparticles ; Transferrin

OBJECTIVETo observe the skin regeneration after hair follicle bulb cells were implanted into collagen/chitosan porous scaffolds in vitro.

METHODSThe cultured dorsal hair follicle bulb cells of 4d-old C57BL/6J mice were implanted into collagen/chitosan porous scaffolds in vitro. The skin regeneration was observed.

RESULTThe skin-like structure was formed on the collagen/chitosan porous scaffolds where were cultured the hair follicle bulb cells before 4th passages.

CONCLUSIONThe skin-like structure is generated in vitro when early passages of cultured hair bulb cells are implanted into collagen/chitosan porous scaffolds.

Animals ; Chitin ; analogs & derivatives ; Chitosan ; Collagen ; Hair Follicle ; cytology ; Mice ; Mice, Inbred C57BL ; Regeneration ; Skin ; cytology ; Tissue Engineering

Chitosan-carboxymethyl-chitosan complex film was prepared by freeze drying. Some tests in vivo and in animal were employed, in order to evaluate it on biology. All results indicated that the film has not only good surface compatibility but also good structural compatibility. It can be more suitable for GTR technology.
Animals ; Biocompatible Materials ; chemical synthesis ; pharmacology ; Chitin ; analogs & derivatives ; Chitosan ; Materials Testing ; Membranes, Artificial ; Rabbits ; Rats ; Skin Irritancy Tests

AS1. 398 neutral protease was immobilized onto carboxymethyl chitosan with glutaraldehyde as cross-linking agent. The effects of pH, time of cross-linking, amount of cross-linking agent and the ratio of enzyme to carrier on the activity of the immobilized enzyme were demonstrated, and the optimum immobilization condition of AS1. 398 neutral protease was established. Also studied was the characterization of immobilized enzyme,including pH, temperature, Km and the stability of storage.
Bacterial Proteins ; chemistry ; Chitosan ; analogs & derivatives ; pharmacology ; Endopeptidases ; chemistry ; Enzymes, Immobilized ; chemical synthesis ; chemistry ; Glutaral ; pharmacology ; Microspheres

In this work a system which consists of chitosan (CS) microcores entrapped within enteric polymer is presented. Vitamin D2, used as a model drug, was efficiently entrapped within CS microcores using spray-drying and then microencapsulated into ethylic cellulose(EC). The morphology and release properties of microcapsules were tested. The influential factors of preparation conditions included molecular weight of chitosan, concentration of chitosan solution, concentration of acetic acid, loading of vitamin D2 were discussed. The results of in vitro release studies showed that the microcapsules prepared in this article could realize sustained release in intestine.
Capsules ; Cellulose ; analogs & derivatives ; pharmacology ; Chitin ; analogs & derivatives ; pharmacology ; Chitosan ; Delayed-Action Preparations ; Drug Compounding ; Drug Delivery Systems ; Ergocalciferols ; pharmacology ; In Vitro Techniques

OBJECTIVETo seek new method for the treatment of peripheral nerve injury.

METHODSIn rat model with sciatic nerve defect, chitosan-collagen film was sutured into conduit to bridge 5 mm, 10 mm nerve defects. Rats that underwent end-to-end anastomosis were taken as controls. General observation, electrophysiological study, histological study and image analysis were performed at 4, 8, 12 weeks postoperatively.

RESULTSIn 5 mm nerve defects, the quality of nerve regeneration was similar to that of the control group. For 10 mm nerve defect, nerve regeneration was inferior to that of the control group. Chitosan-collagen film obviously degraded at 12 weeks postoperatively.

CONCLUSIONSChitosan-collagen film conduit can be used to bridge peripheral nerve defect.

Animals ; Biocompatible Materials ; therapeutic use ; Chitin ; analogs & derivatives ; therapeutic use ; Chitosan ; Collagen ; therapeutic use ; Male ; Models, Animal ; Nerve Regeneration ; Rats ; Rats, Wistar ; Sciatic Nerve ; injuries ; physiology ; surgery

OBJECTIVETo investigate the effect of butyrylchitosan on the expression of proliferating cell nuclear antigen ( PCNA) in fibroblast proliferation of rabbit eyes after filtering operation.

METHODSTwenty-four New Zealand rabbits were randomly divided into 2 groups, with 12 rabbits in each group. Rabbits in one group received butyrylchitosan under scleral patch of trabeculectomy in right eyes and trabeculectomy in left eyes (trabeculectomy group). Rabbits in the other group received mitomycin C (MMC) in trabeculectomy in right eyes (MMC group) and without operation in left eyes. Rabbits were killed 1, 4, and 12 weeks after operations. Immunohistochemical staining was used to detected PCNA expression in fibroblast.

RESULTSAfter use of butyrylchitosan, the PCNA expression significantly decreased compared with trabeculectomy group (P < 0. 001). PCNA expression in MMC group was significantly lower than in trabeculectomy group (P <0. 001).

CONCLUSIONUsing butyrylchitosan under scleral patch of trabeculectomy decreases PCNA expression in proliferating cell and inhibits the scarring at filtering site.

Animals ; Cell Proliferation ; drug effects ; Chitosan ; analogs & derivatives ; pharmacology ; Female ; Fibroblasts ; cytology ; metabolism ; Filtering Surgery ; Male ; Membranes, Artificial ; Proliferating Cell Nuclear Antigen ; biosynthesis ; Rabbits

OBJECTIVETo evaluate the effects of arginine modified chitosan or hexadecylated modified chitosan as gene carriers on the cellular uptake by vascular smooth muscle cells and its in vitro cytotoxicity. METHODS Plasmid DNA was labeled with alpha-32P-dATP and complexed with the modified chitosans or unmodified chitosan to form nanoparticle complexes by complex coacervation method. Uptake of all kinds of chitosan/ DNA nanoparticle complexes (CNC) by A10 cells was measured by beta-liquid scintillation counting. The in vitro cytotoxicity of the CNC was evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay.

RESULTSThe diameters of the CNC ranged from 55.9-174.9 nm and the zeta potentials were from 10. 8 mV for the arginine modified chitosan/DNA nanoparticle complexes (ACNC) to 1.8 mV for the hexadecylated chitosan/DNA nanoparticle complexes (HCNC). The cellular uptake of the modified chitosan/ DNA nanoparticle complexes (MCNC) by A10 cells increased significantly when compared with the unmodified chitosan/DNA nanoparticle complexes (UCNC) (P < 0.05), with the HCNC at N/P ratio of 1:1 and the ACNC at ratio of 8:1 showing the highest cellular uptake (1.3 fold higher than UCNC, P < 0.05). MCNC were much less cytotoxic when compared with Lipofectamine 2000-DNA nanoparticles.

CONCLUSIONDNA nanoparticle complexes prepared with either arginine or hexadecylated modified chitosan can improve the cellular uptake of the DNA, while the in vitro cytotoxicity of both of the modified chitosan is much less than that of Lipofectamine 2000.

Animals ; Antigen-Antibody Complex ; Arginine ; pharmacology ; Chitosan ; chemistry ; pharmacology ; Citric Acid ; analogs & derivatives ; pharmacology ; Cytotoxicity, Immunologic ; DNA ; pharmacology ; Genetic Vectors ; Nanoparticles ; Rats