Synthesis and characterization of Poloxamer 188-grafted heparin copolymer.

BACKGROUND: Poloxamer 188 is a safe biocompatible polymer that can be used in protein drug delivery system. AIM: In this study, a new heparin-poloxamer 188 conjugate (HP) was synthesized and its physicochemical properties were investigated. HP structure was confirmed by Fourier transform infrared spectroscopy (FTIR) and Hydrogen-1 nuclear magnetic resonance spectroscopy ((1)H-NMR). Content of the conjugated heparin was analyzed using Toluidine Blue. The critical micelle concentration (CMC) of the copolymer was determined by a fluorescence probe technique. The effect of HP on the gelation of poloxamer 188 was characterized by the rheological properties of the HP-poloxamer hydrogels. Solubility and viscosity of HP were also evaluated compared with poloxamer 188. RESULTS: From the results, the solubility of the conjugated heparin was increased compared with free heparin. The content of heparin in HP copolymer was 62.9%. The CMC of HP and poloxamer 188 were 0.483 and 0.743 mg/mL, respectively. The gelation temperature of 0.4 g/mL HP was 43.5 degrees C, whereas that of the same concentration of poloxamer 188 was 37.3 degrees C. With HP content in poloxamer 188 solution increasing, a V-shape change of gelation temperature was observed. CONCLUSION: Considering the importance of poloxamer 188 in functional material, HP may prove to be a facile temperature-sensitive material for protein drug-targeted therapy.

Experiment on the feasibility of using modified gelatin nanoparticles as insulin pulmonary administration system for diabetes therapy.

Polymeric nanoparticles are widely used as targeted carriers for biomacromolecules. In this paper, modified gelatin nanoparticles were prepared and their feasibility as insulin pulmonary administration system was investigated. D: ,L: -glyceraldehyde and poloxamer 188 were used for gelatin nanoparticle preparation. Novel water-in-water emulsion technique was used to prepare insulin-loaded nanoparticles. Morphological examination of insulin-loaded nanoparticles was carried out using scanning electron microscopy (SEM). Intratracheal instillation of insulin-loaded nanoparticles was performed to evaluate animal hypoglycemic effect. With fluorescence labeling of insulin, alveolar deposition and absorption of insulin-loaded nanoparticles were investigated. Histological changes in the lung were also observed to evaluate the safety. From the micromorphology observation, insulin-loaded nanoparticles under gelatin-poloxamer 188 ratio at 1:1 showed smooth and uniform surface, with average particle size 250 nm and Zeta potential -21.1 mV. From animal experiment, insulin-loaded nanoparticles under gelatin-poloxamer 188 ratio at 1:1 promoted insulin pulmonary absorption effectively and showed good relative pharmacological bioavailability. Proved by alveolar deposition result, FITC-insulin-loaded nanoparticle group was characterized by an acute and rapid hypoglycemic effect. In addition, nanoparticles could guarantee the safety of lung by reducing insulin deposition in lung. A transient weak inflammatory response was observed at 1 day after administration. With good physical characterization, high bioavailability, fast and stable hypoglycemic effect, insulin-loaded nanoparticles might be developed as a novel insulin pulmonary system for diabetes therapy.

Characterization and anti-tumor activity of chemical conjugation of doxorubicin in polymeric micelles (DOX-P) in vitro.

Characterization and anti-tumor activity of chemical conjugation of doxorubicin (DOX) in polymeric micelles were investigated. Polymeric micelles with chemical conjugation of doxorubicin (DOX-P) were prepared. Succinic anhydride activated pluronic F68 was first synthesized and the primary amine group in doxorubicin was conjugated to the terminal carboxyl of pluronic F68 via a amide. The resulting polymeric micelles in aqueous solution were characterized by measurement of size, ξ-potential, drug loading and critical micelle concentration. From characterization results, DOX-P micelles had superiorities over physically-loaded DOX micelles in loading efficiency, diameter and CMC value. From drug release experiment in vitro, DOX-P micelles reached a sustained release profile for DOX. The cytotoxic activity of the micelles against A549/DOX cells was greater than free DOX. Fluorescence microscope observation and flow cytometry analysis supported the enhanced cellular uptake of the micelles. From A549/DOX cells experiments, DOX-P micelles could enhance DOX anti-tumor activity and circumvent the multi-drug resistance (MDR) of A549/DOX cells. With low CMC value, high loading efficiency, nanometer diameter, good penetration ability and controlled release behaviour, DOX-P micelles might be developed as a new cancer targeted delivery system.

[Comparison of the clinical effects between gold-alloy post-core-crowns and nickel-chromium-alloy post-core-crowns].

PURPOSE: To evaluate the clinical effects between gold-alloy post-core-crowns and nickel-chromium-alloy post-core-crowns. METHODS: Four hundred incisors, canines and premolars from 289 patients were selected. The crown had been destroyed seriously and root canal therapy was carried out. The root canal and the surface of the root were prepared well, then silicone impression material was injected into the root canal and the prepared plastic pin was inserted. Precise impression was taken and divided into two groups randomly. Group A was restored by gold-alloy post-core-crowns, while Group B was restored by nickel-chromium-alloy post-core-crowns. The patients were followed up for 3 years, the clinical effects were evaluated and compared using SPSS10.0 software package for Chi-square test. RESULTS: There was no significant difference(P>0.05) of maintenance rate between the two groups, but there was significant difference (P<0.05) in the occurence of inflammation and staining of gingiva. CONCLUSION: Gold-alloy post-core-crown is more suitable for restoration of teeth defects than nickel-chromium-alloy post-core-crown. Supported by Research Fund of Medical Science and Technology of Guangdong Province (Grant No. WSTJJ20070101310103196603041632).