Bone-targeting drug delivery system of biomineral-binding liposomes loaded with icariin enhances the treatment for osteoporosis.

BACKGROUND: Osteoporosis is a bone-incapacitating malady and it is characterized by obvious bone mass loss and bone microarchitecture deterioration. Current treatments for osteoporosis have many limitations, including the non-obvious therapeutic effect and long-term safety issues. Icariin is a pharmacologically active flavonoid glycoside, which shows potential application in treatment of osteoporosis. But its clinical application is limited by the inherent disadvantages such as poor water solubility, first pass effect after oral administration, and low bioavailability. Moreover, due to lack of targeting ability, icariin cannot accumulate at the local diseased region to provide early protection from fractures. To solve the application problems of icariin and enhance its therapeutic effects on osteoporosis, this work aimed to design a targeting drug delivery system of biomineral-binding liposomes (BBL) mediated by pyrophosphate ions. RESULTS: Biomineral-binding liposomes enhanced the binding ability of liposomes with hydroxyapatite particles. It increased the serum level of alkaline phosphatase and reduced that of tartrate-resistant acid phosphatase 5b. Meanwhile, BBL increased the mechanical strength of femoral midshaft, preserving the trabecular bone microarchitecture. Moreover, BBL could initiate bone turnover/remodeling of rats with osteoporosis. CONCLUSIONS: This drug targeting delivery system of BBL loading with icariin showed more therapeutic advantages than the free icariin for the treatment of osteoporosis, which may be a kind of valid candidate in future osteoporosis therapy.

Awareness, attitude and behavior regarding proton pump inhibitor among medical staff in the Southwest of China.

BACKGROUND: Proton pump inhibitors (PPIs) are one of the most frequently prescribed classes of drug in the world and there is a growing number of publications on correct versus incorrect use of PPIs worldwide. The knowledge of PPIs among the medical staff is essential for improving the rationality of PPI application. The present study aimed to investigate awareness, attitude and behavior toward PPI use among medical staff in the Southwest of China. METHODS: The present descriptive-analytical study was conducted on 900 medical staff from three professional groups (300 doctors, 300 nurses and 300 pharmacists) in China. The study data were collected through a self-designed questionnaire which included demographics, awareness, attitude and behavior toward PPI use. The study was carried out in 22 hospitals in Luzhou between February and June 2018. RESULTS: Of 900 surveys issued, 851valid questionnaires (295doctors, 268 nurses and 288 pharmacists) were returned. Of all respondents, 33.25% were men and 66.75% were women. The score related to PPI awareness score of medical staff was low (59.47 ± 15.75). The level of awareness of pharmacist was significantly higher than that of doctors and nurses (P < 0.01), which was related to gender, age, occupation, educational level, professional title, hospital nature and hospital grade. Similarly, on the attitude towards PPI use, the pharmacists scored also significantly higher than doctors and the nurses (P < 0.01). Three hundred eighty-one of 851 medical staff had used PPI in the past 1 year, of which omeprazole was the most widely used. Among doctors, nurses and pharmacists, the usage rate of PPI was 50.85, 42.16, 40.97%, respectively. The use frequency was related to occupation and professional title. The score about the behavior toward PPIs of the nurses was also significantly lower than that of doctors and pharmacists (P < 0.01). CONCLUSIONS: The study indicated that the medical staff lack of awareness concerning rational use of PPI in China, especially nurse. Thus, it is necessary to call for action on the improvement of PPI awareness and medication-taking behaviors to reduce PPI overuse and to promote the rationality of PPI application.

[Effect of Recombinant Human Thrombopoietin (rhTPO) on Hematopoietic Reconstitution in Allogeneic Hematopoietic Stem Cell Transplantation Model].

OBJECTIVE: To explore the effect of recombinant human thrombopoietin (rhTPO) on hematopoietic reconstruction in allogeneic hematopoietic stem cell transplantation (allo-HSCT) model. METHODS: The C57BL/6 mice were employed as the donors, and BALB/c mice as recipients. The bone marrow mononuclear cells of the donor mice were extracted and pretreated, which then were injected with 5×106 per mouse through the tail vein of the recipient to establish an allo-HSCT model. The implantation of hematopoietic stem cells in the recipient mice was detected by flow cytometry on the 28th day after transplantation. Next, the successfully modeled recipient mice were randomly divided into experimental group and control group. The rhTPO was injected into mice in the experimental group on the first day after transplantation, while the saline was injected into mice in the control group. Both groups were injected for 14 consecutive days. The peripheral blood and bone marrow hematopoiesis of the two groups were observed on day 1, 3, 7, 14, and 21 after transplantation. RESULTS: The expression rate of H-2Kb in the bone marrow of recipient mice was 43.85% (>20%) on the 28th day after transplantation, which indicated that the recipient mice were successfully chimerized. Meanwhile, counts of PLTs on the day 3, 7, 14, and 21 after transplantation in the experimental group were higher than those in the control group with statistical significances (P<0.05). In addition, hematopoietic function of bone marrow was suppressed in both groups on day 1, 3 and 7 after transplantation, but hematopoietic bone marrow hyperplasia was better in the experimental group than in the control group. On day 14 and 21 after transplantation, the hematopoietic function of bone marrow in the two groups was recovered, and the experimental group showed more obvious than the control group. CONCLUSION: rhTPO can effectively stimulate the production of PLTs and facilitate the recovery of white blood cells and hemoglobin after allo-HSCT, and promote hematopoietic recovery and reconstitution of bone marrow.

GX1-mediated anionic liposomes carrying adenoviral vectors for enhanced inhibition of gastric cancer vascular endothelial cells.

Gastric cancer is a highly lethal malignancy and its 5-year survival rate remains depressed in spite of multiple treatment options. Targeting drug delivery to tumor vasculature may be a promising strategy for gastric cancer therapy, for it can block the nutrition source of tumor and inhibit the metastasis and invasion in a certain extent. In present study, we have prepared the drug-targeting delivery system of peptide GX1-mediated anionic liposomes carrying adenoviral vectors (GX1-Ad5-AL), in which the tumor suppressor gene of PTEN was integrated into DNA of Ad5 and the GX1 peptide could play targeting role to vascular of gastric cancer. The inhibition ability of GX1-Ad5-AL to human gastric cancer cell lines (SGC-7901) and human umbilical vein endothelial cells (HUVEC) was evaluated by MTT assay. Further, the cell migration assay was carried out in transwell inserts and the cells uptaking of GX1-Ad5-AL was detected by confocal laser scanning microscopy. The experimental results indicated that the average cell proliferation inhibition rates resulted from the drug delivery system of GX1-Ad5-AL in SGC-7901 and HUVEC were 68.36% and 64.13%, respectively which were higher than that resulted from GX1 or Ad5-AL. Meanwhile, results of cell migration experiment demonstrated that GX1-Ad5-AL could significantly suppress the migration of gastric cancer cell of SGC-7901. Moreover, both the imaging from confocal laser scanning microscopy and the quantitative analysis of fluorescence intensity showed that, GX1-Ad5-AL was more easily uptaken by SGC-7901 cells, as compared to Ad5-AL. Therefore, the formulation of GX1-Ad5-AL was effective for enhancing the inhibition effect and suppressing the migration of gastric cancer vascular endothelial cells.