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

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

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

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

AIMTo investigate the formation mechanism, macromolecular drug loading capacity and release property of alginate-chitosan microcapsules (ACM).

METHODSACM was prepared by emulsification-gelation method and its formation mechanism was studied by DSC analysis. Using bovine serum albumin (BSA) as model drug, the drug loading and release properties of the microcapsules on macromolecular drug were investigated.

RESULTSThe results of DSC analysis showed that there is electrostatic interaction between materials encapsulated in the microcapsule. With the increase of BSA microcapsule ratio, the BSA loading percentage rose from 9.20% to 35.08%; and with the ascent of chitosan (CTS) concentration, the BSA loading percentage increased from 30.29% to 38.12%. The BSA microcapsules whowed a two-phase release in both 0.1 mol.L-1 HCl and phosphate buffer saline (pH 7.4). With the increase of CTS concentration, the BSA release more and more slowly in 0.1 mol.L-1 HCl.

CONCLUSIONSpheric and well-dispersed alginate-chitosan microcapsules were prepared. The microcapsule showed good loading capacity to BSA as well as sustained release to a certain degree.

Alginates ; chemistry ; Biopolymers ; Calorimetry, Differential Scanning ; Capsules ; Chitin ; analogs & derivatives ; chemistry ; Chitosan ; Delayed-Action Preparations ; Drug Carriers ; Drug Delivery Systems ; Serum Albumin, Bovine ; administration & dosage ; Technology, Pharmaceutical ; methods

Animals ; Cations ; chemistry ; Chitin ; administration & dosage ; analogs & derivatives ; chemistry ; Chitosan ; DNA ; administration & dosage ; Gene Transfer Techniques ; Genetic Therapy ; Liposomes ; administration & dosage ; chemistry ; Polylysine ; administration & dosage ; chemistry

Objective proteins synthesized from genetically recombined Escherichia coli strain (E. coli) have been successfully produced by microbe fermentation, but complicated separation and purification steps always make against the maintenance of activities as well as increase the cost. Aiming at simplifying the process, an idea of administrating directly the microencapsulated genetically recombined E. coli is proposed. In this paper, study on culture of E. coli DH5 alpha immobilized in alginate/chitosan (ACA) microcapsule is presented. It was found that E. coli DH5 alpha grew well in the microcapsule with stable growth period longer than that of suspension culture, and cell aggregation phenomenon was observed. In vivo experiments showed that ACA microcapsules with E. coli DH5 alpha stayed over 48 h in mouse intestine, and the morphology of microcapsules was kept intact. These preliminary results have demonstrated that administration of microencapsulated E. coli DH5 alpha is safe, which laied the foundation for microencapsulated genetically recombined E. coli as carriers of gene engineering drugs.
Alginates ; Animals ; Capsules ; Chitin ; analogs & derivatives ; Chitosan ; Drug Delivery Systems ; Escherichia coli ; growth & development ; physiology ; Gene Transfer Techniques ; Glucuronic Acid ; Hexuronic Acids ; Mice