Aim: To prepare ropivacaine hydrochloride multivesicular liposomes, and to study the physicochemical properties and drug release behavior in vitro. Methods: Ropivacaine hydrochloride multivesicular liposomes were prepared by the multiple emulsion method. Single factor experiments were utilized to study the factors which affect the encapsulation efficiency of multivesicular liposomes. The formulation and pharmaceutical process were optimized by Box-Behnken experimental design, with the factors of encapsulation efficiency as the criteria. Three batches of the optimized multivesicular liposomes were prepared, and the encapsulation efficiency and in vitro release behavior were studied. Results: The particle size of the optimized multivesicular liposomes was uniform and 85% of them were well distributed in the range of 7-30 μm. The encapsulation efficiency was up to 90% when the ratios of lipid to drug, phospholipids to cholesterol and the amount of triolein was 1. 328:1(w/w) ,1.5: 1(w/ w) and 6 mmol/L, respectively. The release profile in vitro fitted to a first-order kinetics with the period of release up to 48 h in PBS buffer under 37 ℃. Conclusion: Ropivacaine hydrochloride multivesicular liposomes showed high encapsulation efficiency and significant sustained-release feature.

In this study, indomethacin (IND) loaded solidified-polymeric micelles (IND-SPM) were prepared. Their in vitro characteristics were investigated. Methoxy-poly(ethylene glycol) poly(D, L-lactide) copolymer (mPEG-PDLLA) was used as IND carrier. The preparation of IND-SPM was conducted by solution-absorption method and evaporation by rotary evaporator. Polyplasdone XL-10 was used as adsorbent. The solution-absorption method was conducted by the following procedure; IND and mPEG-PDLLA were dissolved in acetone, followed by addition of polyplasdone XL-10 and stirred to obtain a suspension. The powder of IND-SPM was simply obtained after the organic solvent was completely evaporated. More than 90% (w/w) of IND (20 mg) in the powder was dissolved in 250 mL PBS within 30 min. DSC, 1H NMR and SEM results proved that IND was encapsulated within mPEG-PDLLA. The solubility of IND in the system increased 4.6 times with the highest amount of copolymer. The solidified particles were found to be suitable for the formulation of tablets or capsules.

Objective To explore the induction of basic fibroblast growth factor (bFGF)-chitosan carrier transforming the adult rat bone marrow mesenchymal stem cells (rMSCs) into nerve cells. Methods rMSCs were detected qualitatively and counted quantitatively by immunohistochemistry after they were induced into nerve cells, such as neural stem cells neurons and astrocytes. The methyl thiazolyl tetrazolium (MTT) chromometry assay was carried out to determine the cell viability. Results rMSCs induced by bFGF-chitosan carrier expressed neural stem cell marker nestin, neuron marker β-tubulin Ⅲ and astrocytes marker glial fibrillary acidic protein (GFAP). Nestin expressed more in the bFGF-chitosan group, and reached its maximum (49.40%) at the 9th day. Conclusion bFGF-chitosan carrier can induce the adult rMSCs differentiate into neural stem cells in a high proportion.

Graft copolymerization is one of the most effective methods to improve the performance of pullulan and extend its applications. This paper attempts to review the recent progresses in the preparation and application of graft copolymers of pullulan as pharmaceutical carriers from different synthesized polymers and the properties of graft copolymers of pullulan. The problems of pullulan based graft copolymers in drug release system are expounded, and the future development in this field direction is presented.

This study is to prepare the in situ forming sustained-release injection which can perform sustained release behavior at the periodontal site for 7 days and to evaluate its in vitro and in vivo properties. After preparation of in situ forming sustained-release injection the in situ time was studied. And the surface of the solid injection was characterized by SEM. The rheological curve at 0 degrees C, 25 degrees C, 37 degrees C was determined and the impact of the temperature on the viscosity was examined. The in vitro release behavior was investigated. At last, rabbit periodontitis model was established to study its pharmacokinetics. The injection was stable, hard to stratify and decompose. The in situ forming time was about 6 seconds. It can easily adhere into periodontal pockets. There were lots of holes on the surface of the solid injection for the drug to diffuse. The drug releasing curves could be fit by Korsmeyer-Peppas equation. The drug smoothly released for 7 days at pH 7.4 PBS buffer with a very slight burst release and maintained a certain concentration. In vivo pharmacokinetics results indicated that after administration with the in situ forming injection, achievement of tinidazole (TNZ) concentration in gingival crevicular fluid (GCF) was more comparable and long-lasting than usual solution of TNZ management and relatively constant TNZ levels were attained until 168 h. All these results supported the prospect of tinidazole in situ forming sustained-release injection in clinical applications.

An HPLC pre-column derivatization detection method was established to detect and analyze the formaldehyde and acetaldehyde in polysorbate 80 and polysorbate 20 from different manufacturers.The effects of aldehyde and acetaldehyde on the aggregation of adalimumab under different conditions were monitored.Based on the control of genotoxic impurities and the influence on the stability of monoclonal antibody preparations, the control limits of the two chemicals were preliminarily obtained.2, 4-dinitrophenylhydrazine (2, 4-DNPH) was applied as the derivatization reagent in HPLC pre-column derivatization; acetonitrile and water were used as mobile phase to perform a gradient elution on a C8 (4.6 mm × 150 mm, 5 μm) chromatographic column.The detection wavelength was 360 nm, and the external standard method was used for quantification.Verification results showed that the method was suitable for the quantitative analysis of trace formaldehyde and acetaldehyde in polysorbate 80 and polysorbate 20 . The detection and analysis of formaldehyde or acetaldehyde in different batches of polysorbate 80 and polysorbate 20 from different manufacturers showed that the content of formaldehyde and acetaldehyde were quite different. The content of formaldehyde and acetaldehyde in polysorbate 80 were significantly higher than those of polysorbate 20. After monitoring the changes of adalimumab aggregates treated by formaldehyde and acetaldehyde by size exclusion chromatography (SEC), it was found that the effect of formaldehyde on adalimumab aggregation was significantly higher than that of acetaldehyde.According to the requirements of ICH M7 (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, M7: Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk), the impurity limits of formaldehyde and acetaldehyde in polysorbate 80 and polysorbate 20 for monoclonal antibody preparations were calculated from the perspective of risk assessment.Combined with the influence on the aggregation stability of monoclonal antibodies, the preliminary limis for acetaldehyde and acetaldehyde were recommended to be ≤ 7 μg/g and ≤ 765 μg/g, respectively.

Taking plastic packaging materials as an example, this paper mainly summarizes the general principles of pharmacopoeias and guiding principles of relevant government departments related to the compatibility studies of drugs and packaging materials at home and abroad, with much reference to relevant monographs and literature. The purpose and specific methods of extraction and interaction studies are summarized and discussed. The existing problems and solutions in compatibility research are also proposed in this review to provide some refe-rence for researchers in relevant fields.

To conduct the characterization of its pharmacokinetics in rats of nifedipine sustained-release pellets and to study the relationship between the pellets and CYP3A4 activity. A gradient HPLC method was developed to simultaneously determine 6β-hydroxycortisol and hydrocortisone. CYP3A4 activity of rats was quantified by urinary ratio of 6β-hydroxycortisol/hydrocortisone after intravenous injection of hydrocortisone as a biomarker. HPLC method was also developed to quantify the drug concentration in plasma of rats, and the studies of pharmacokinetics were performed after oral administration of single dose of two formulations: Nifedipine matrix sustained-release pellets and nifedipine tablet(using as control). The results showed that the ratio of ten rats was 0. 271±0. 129. cmax of nifedipine sustained-release pellets decreases by nearly 70%, tmax significantly increased by 400% and t1/2 and MRT significantly increased by 230% compared to control. Nifedipine sustained-release pellets had a significant sustained-release property compared to the control and CYP3A4 activity affected its pharmacokinetics behavior.

The aims of this research were to constitute and evaluate one targeting anticancer co-delivery system for both micro-molecularchemotherapeutic drugs(docetaxel, DTX)and small interfering RNA(siRNA)expressed by COX-2. The nanoparticles composed of poly(D, L-lactide-co-glycolide)(PLGA)bearing disulfide-linkaged reducible polyethyleneimine(PEIss)covered by hyaluronic acid(HA). Meanwhile, HA-PEI-PLGA nanoparticles were prepared as control. Firstly, the solvent evaporation was used to the particles which exhibited a core-shell structure with a uniform size of 150-200 nm. The cumulative drug release in two kinds of PBS media(pH 7. 4 and pH 5. 0)during 72 hours indicated that DTX-loaded nanoparticles had sustained-release effect within 24 hours. The cumulative release of DTX of HRPSP NPs in PBS pH 5. 0 was 10%-25% more than that in PBS pH 7. 4, which demonstrated that favored release of DTX from nanoparticles could be achieved in acidic tumor microenvironment. Then, the highest transfection efficiency was observed after 14-16 h incubation at N/P ratio of 40/1. Following the saturation of CD44 receptor, the mean fluorescence intensity of HRPSP NPs from the cells decreased drastically in the case of saturation with free HA before. However, there existed no significance in the fluorescence of RPSP NPs between the cells with and without saturation with free HA, which indicated the nanoparticles′ targeting potential toward tumor cells. In the Western blot, the relative silencing efficiency of Bcl-2, bax, capase-3 and COX-2 mRNAprotein was calculated. In comparison to the control group, the silence efficiencies of bax and capase-3 were both significantly increased while that of Bcl-2 was evidently reduced, particularly in siCOX-2/HRPSP NPs group(P< 0. 01). The similar results were obtained in the silence efficiency of COX-2 protein in which the COX-2 quantity on mRNA and protein decreased. The results suggest that the nanoparticles could achieve the synergistic effect on the combinatorial delivery of siRNA and lipophilic anti-tumor drugs.

Objective To investigate the expressions of platelet activation-dependent granule membrane protein and platelet-derived growth factor receptor-αB, and the ultra-microstructure changes of platelets in patients with acute ST-segment elevation myocardial infarction(STEMI). Method The expressions of platelet activationdependent granule of glycoprotein (CD62P)and platelet derived growth factor receptor αβ subtype (PDGFR-αβ)of platelets in peripheral blood in 36 patients with acute ST-segment elevation myocardial infarction(STEMI) hospitalized and another 34 healthy subjects over the same period (control group) were investigated by flow cytometry and data were analyzed. The changes of ultra microstructure and activity of blood platelets in those patients and control group were observed under the scanning electron microscope. Results The expressions of CD62P and PDGFR-αβin patients with STEMI group before treatment were (3.65 ± 1.87) % and (0.43 ± 0.39) %, respectively, and those after treatment were (0.96 ± 0.79) % and (0.28 ± 0. 24) %, respectively, whereas those in control group were (0.67 ± 0.35) % and (0.27 ± 0.22) %, respectively, which were much lower in control than those in patients with STEMI before treatment (P ＜ 0.01 or P ＜ 0.05) respectively. There were statistically significant differences in the expressions of CD62P and PDGFR-αβ in patients group between pre-treatment and posttreatment (P ＜0.01 or P ＜0.05), respectively. Obvious ultra-microstructure changes of platelet surface in patients with STEMI group were observed. Conclusions Due to platelet activation in AMI, the expressions of CD62P can be used as effective indicators for monitoring coronary heart disease, and the PDGFR-αβ can be used as a reference indicator. The platelet surface ultra-microstructure changes during platelet activation in patients with AMI can be found by scanning electron microscopy.