Synthesis of tacrolimus nanocrystals and artificial tears surface modification / 国际生物医学工程杂志

Objective To synthesize a dual-function nanodrug with immunosuppression of tacrolimus (FK506) and lubrication of artificial tear carboxymethylcellulose sodium (CMC), and provide a basis for the clinical treatment of dry eye syndrome. Methods The FK506 nanocrystals were prepared by ultrasonic method, and polyallylamine hydrochloride (PAH) and CMC were deposited alternatively on the surface of FK506 nanocrystals using layer-by-layer (LbL) self-assembly technology to prepare the bifunctional nanodrug. The morphology, particle size, surface charge, and composition of the nanodrug were analyzed. Results The particle size of FK506 nanocrystals was uniform, and the FK506-(PAH/CMC)3 was approximately spherical with uneven surface. Zeta potential detection results showed that the charge changed alternatively with the increasing of layer number. The results of laser scanning confocal imaging and infrared spectroscopy showed that PAH and CMC were successfully modified on the surface of FK506 nanocrystals. Conclusion The prepared FK506-(PAH/CMC)3 nanodrug is expected to provide a scientific basis for the combined treatment of dry eye.

Optimization of the Processing Technology of Rehmanniae Radix Praeparata by Muti-indexes Integrating Score-Orthogonal Test / 中国药房

OBJECTIVE:To optimize the processing technology of rehmanniae radix praeparata. METHODS:Using transfer rates of catalpol,rehmaionoside D,acteoside,isoacteoside,polysaccharide as indexes for comprehensive score,heating tempera-ture(pressure),heating time and heating times as investigating factors,L9(34)orthogonal test was used to optimize the processing technology of rehmanniae radix praeparata,and verification test was conducted. RESULTS:The optimal processing technology of rehmanniae radix praeparata was as follow as heating temperature of 125 ℃,pressure of 150 kPa for twice,2 h every time. The comprehensive scores of 3 batches of samples were 0.6985,0.6755,0.7016 in the verification test,respectively,RSDs were less than 5%(n=3). CONCLUSIONS:Optimized processing technology is simple,stable,feasible,and can provide reference for in-dustrial production of rehmanniae radix praeparata.

Cellular uptake of Tumor-targeted nanoparticles derived from pullulan acetate conjugate / 医学研究生学报

Objective Folate receptors ( FRs) , overexpressed on the surface of a variety of tumor cells , are potential targets for tumor targeting therapy .This study aimed to prepare an FR-mediated drug nanocarrier with folate conjugated pullulan acetate ( FPA) to target chemotherapeutic agents to FR-overexpressed tumor cells and investigate its tumor-suppressing effect in vitro. Methods The cytotoxicity of epirubicin-loaded FPA nanoparticles ( FPA/EPI NP) against HepG2 and Hela cells was evaluated by MTS assay.The HepG2 and Hela cells were divided into five groups to be treated with NPs (NP control), chlorpromazine, chloro-quine, amiloride, and folate, respectively, followed by detection of the fluorescence intensity by flow cytometry . Results FPA/EPI NP was successfully formulated into NPs , with the mean particle size of (268.5 ±12.0) nm, by dialysis with an almost spherical shape . The drug-loading rate and entrapment rate of FPA/EPI NP were (6.45 ±1.04) and (72.45 ±11.50) %, respectively.The survival rates of the HepG2 and Hela cells were both >95%after 24 hours of incubation with FPA NP at 5, 40, 200, 400 and 1000μg/mL and 90.0%after 72 hours.The survival rates of the HepG2 cells treated with 5, 40, 200, 400 and 1000μg/mL FPA/EPI NP for 24 hours were (92.3 ±5.2), (70.4 ±4.6), (50.0 ±4.0), (41.1 ±4.1) and (27.0 ±3.6) %, respectively.Compared with the NP control group, the Hela cells of the chlorpromazine , amiloride and folate groups showed a significantly lower rate of NP uptake (P<0.05), and so did the HepG2 cells pretreated with chlorpromazine or amilo-ride (P<0.05).At 72 hours, the half maximal inhibitory concentrations (IC50) of FPA/EPI NP against HepG2 and Hela cells were 168 and 105μg/mL, respectively . Conclusion Clathrin-mediated endocytosis and macropinocytosis are involved in the internaliza-tion of FPA/EPI NP in HepG2 cells, while clathrin-and FR-mediated endocytosis in that of Hela cells .FPA NP may serve as a new drug carrier for tumor-targeted therapy .

Advances of bone substitute materials for alveolar ridge preservation / 国际生物医学工程杂志

Alveolar ridge preservation (ARP) can prevent alveolar bone resorption,promote new bone formation and maintain the hard and soft tissue morphologies of tooth socket after tooth extraction,which plays an important role in the field of oral implantology.ARP has become a hot topic in dental research with the rapid development of bone substitute materials.This review focuses on recent development of various bone filling materials as well as future perspective of biomedical materials for ARP.

The efficacy and safety of low-dose tiotropium bromide inhaled via Respimat(R) in patients with chronic obstructive pulmonary disease / 中华内科杂志

Objective To compare the efficacy and safety of long-term treatment (48 weeks) with tiotropium bromide (5 μg) via Respimat(R) with placebo in patients with chronic obstructive pulmonary disease (COPD).Methods A total of 338 patients were randomized in this double-blind,placebo controlled,parallel study.All patients received either tiotropium bromide or placebo.Tiotropium bromide solution 5 μg (2 × 2.5 μg/puff) or matching placebo was delivered via Respimat(R) at a dosage of once daily for 48 weeks.Co-primary endpoints were trough forced expiratory volume in one second (FEV1) and the time to first exacerbation.Results Statistically significant improvements of both trough FEV1 and trough forced vital capacity (FVC) in the tiotropium group were achieved at weeks 4,24,and 48 compared with those in the placebo group(P ＜ 0.000 1).Tiotropium treatment delayed the time to first exacerbation.The time was 157 days in the tiotropium group and 85 days in the placebo group.A statistically significant difference (P =0.002 7) in favor of tiotropium was also observed.The total numbers of exacerbation during treatment were 90 and 128 in the tiotropium and placebo groups,respectively.The Poisson regression analysis gave a mean exacerbation rate per patient year exposure of 0.67 in the tiotropium group compared to 0.98 in the placebo group with a rate ratio of 0.69 (95％ CI O.50-0.93,P =0.016 4).A much larger improvement from baseline in St.George's respiratory questionnaire (SGRQ) total score was observed for the tiotropium group than in the placebo group(P =0.036 7),SGRQ symptom and activity scores of patients in the tiotropium group were also superior to those of patients receiving placebo.The drugs-related adverse events in the tiotropium and placebo groups were 12 cases and 11 cases,respectively.Conclusions Tiotropium significantly improved lung function and quality of life,delayed the time to first exacerbation,reduced the number of exacerbation.Overall,tiotropium was well tolerated.