Preparation of hispidulin chitosan microsphere and its antiproliferation effect / 中国中药杂志

Hispidulin(HPDL) chitosan microspheres were prepared in this study to deliver HPDL to the lesion sitevia intravenous injection, and further evaluate their anticancer effects in vitro and the growth inhibition effect on A549 cells spheroids. HPDL chitosan microspheres were prepared by emulsion crosslinking method with chitosan as a drug carrier and the amount of HPDL was determined by high performance liquid chromatography (HPLC). The morphology of microspheres was observed under laser scanning confocal microscope. Additionally, the drug release amount of targeting microspheres was detected by dialysis method. Furthermore, the anti-proliferative effects against A549 lung cancer cells were tested by sulforhodamine B (SRB) method, and the effects of HPDL chitosan micrpsphereson early apoptosis of A549 cellswere determined by flow cytometry. A549 cells tumor spheroids were developed in vitro and then HPDL chitosan microspheres were added. On the 0, 1, 3, 7 d after adding the drugs, the inverted microscope was used to observe the mythologicaland volume changes of A549 cells spheroids. The encapsulation efficiency of HPDL chitosan microspheres was （75.32±0.52）%, and the drug loading amount was （7.76±0.67）%. Meanwhile, the microspheres were round shaped andhad smooth surface. The HPDL chitosan microspheres exhibited stronger inhibitory effects on A549 lung cancer cells. The results of flow cytometry indicated that, the early apoptosis rate of lung cancer A549 cells was （37.0±0.75）% at 24 h cells culture after drug administration. The volume of tumor spheroid was significantly inhibited, which had been shrunk by (50.09±11.06)% after the treatment by drug-loaded microsphere at day 7 as compared with blank group; meanwhile, the cells surface were obviously lysed. The preparation method in this research was simple and practicable, and the microspheres prepared with this method were round and smooth, with high encapsulation efficiency, which can significantly inhibit proliferation of lung adenocarcinoma A549 cells and induce cell apoptosis, and at the same time can cause lysisand death of A549 cell tumor spheroid.

Construction of the brain-targeting drug carrier through imprinting of nicotinic acetylcholine receptor α7 / 药学学报

In this study, a novel brain-targeting carrier was made via conformational epitope imprinting. Acrylamide and N,N'-methylene bisacrylamide was used as carrier materials and the N-terminal epitope of nicotinic acetylcholine receptor α7 (nAchR α7) was tested as a template molecule, and the polymer nanoparticles were obtained after polymerization and template removal. The nanoparticles were investigated by particle size analyzer and transmission electron microscopy (TEM). Their targeting capabilities were investigated with a cell uptake assay in vitro and fluorescence imaging in vivo. The results suggest that the nanoparticles had a small particle size (42.1±4.3 nm) with a homogeneous distribution, and good targeting properties in vitro and in vivo. We have made the molecularly imprinted polymer nanoparticles with brain targeting capability, which represents a new tool in the treatment of brain diseases.

Co-delivery of paclitaxel and cyclosporine by a novel liposome-silica hybrid nano-carrier for anti-tumor therapy via oral route / 药学学报

In this study, we developed a novel liposome-silica hybrid nano-carrier for tumor combination therapy via oral route, using paclitaxel and cyclosporine as a model drug pair. Optimization of the preparation of the drug-loading formulation and characterization of its physicochemical parameters and drug release profile were performed in vitro. Then in vivo pharmacodynamics and pharmacokinetics studies were performed. The results showed that the obtained formulation has a small particle size (mean diameter of 100.2 +/- 15.2 nm), a homogeneous distribution [the polydispersity index was (0.251 +/- 0.018)] and high encapsulation efficiency (90.15 +/- 2.47) % and (80.64 +/- 3.52) % for paclitaxel and cyclosporine respectively with a mild and easy preparation process. A sequential drug release trend of cyclosporine prior to palictaxel was observed. The liposome-silica hybrid nano-carrier showed good biocompatibility in vivo and co-delivery of cyclosporine and paclitaxel significantly enhanced the oral absorption of paclitaxel with improved anti-tumor efficacy, suggesting a promising approach for multi-drug therapy against tumor and other serious diseases via oral route.

Exogenous opioid peptide preconditioning in prevention of pulmonary ischemia-reperfusion injury in pigs after cardiopulmonary bypass / 第二军医大学学报

Objective: To evaluate the protective effect of δ-opioid peptide, [D-Ala2-D Leu5]-enkephaline (DADLE), on pulmonary ischemia-reperfusion (I-R) injury after cardiopulmonary bypass (CPB), and to discuss the possible mechanism. Methods: Twenty-eight male pigs were evenly randomized divided into 4 groups, namely, the sham operation group, the CPB group (only subjected to CPB), the DADLE pretreatment group (received DADLE 1 mg · kg-1 before CPB), and the Glibenclamide group (received DADLE 1 mg · kg-1 and glibenclamide 1 mg · kg-1 before CPB). Peak inspiratory pressure (PIP), PaO2, and the plasma malondialdehyde (MDA) concentration were measured in each group before CPB and 10 min, 30 min, and 60 min after reperfusion. The changes of lung tissue wet weight/dry weight ratio (W/ D) were calculated before CPB and 60 min after reperfusion. The animals were sacrificed 60 min after reperfusion to observe the ultrastructural changes of the lungs and to quantitatively assess lung tissue damage (LTD). Results: There were no significant differences among the 4 groups before CPB and the parameters in sham-operation group had no changes at all specified time points. One hour after reperfusion, the PIP, MDA, W/D, and LTD values in Glibenclamide and CPB groups were significantly higher than those in sham-operation and DADLE groups while the PaO2 was significantly lower(P<0.05 or 0.01). There were no significant differences between parameters of sham-operation and DADLE groups except for LTD(P<0.05). There were no significant differences between parameters of Glibenclamide and CPB groups. Histological examination demonstrated that the degree of lung injuries in sham-operation and DADLE groups were slighter than those in Glibenclamide and CPB groups. Conclusion: It suggests that DADLE may exert its protective effect on the lung through opening ATP-sensitive K+ channels, so as to alleviate the lung I-R injury after CPB.

Jugular bulb oxygen saturation during desflurane and isoflurane anesthesia in pa tients undergoing brain tumor surgery / 第二军医大学学报

Objective: To investigate jugular bulb venous oxyg en partial pressure(PjO2)， hemoglobin saturation (SjO2) and the arterial t o jugular bulb venous oxygen content difference(AjDO2) during anesthesia with desflurane and isoflurane in patients with brain tumor. Methods: Fifty-six patients with brain tumor were randomized into desflur ane or isoflurane for maintaining anesthesia. PjO2, SjO2 and AjDO2 in pati ents were measured during normoventilation, hyperventilation and hypoventilation . Results: During normoventilation， SjO2 and PjO2 in desflu rane group was significantly higer than those in isoflurane group（P<0.05 or P<0.01）, and AjDO2 in desflurane group was significantly lower than that in isoflurane group（P<0.05）.Except that PjO2 in desflurane group was si gnificantly higer than that in isoflurane group during hyperventilation （P< 0.01）, there were no differences in SjO2, PjO2 or AjDO2 between the 2 g roups during hyperventilation or hypoventilation. While anesthesia with desflura ne and isoflurane, there was a positive correlation between PaCO2 and SjO2. Conclusion: At the same anesthetic effect concentration, desflur ane can significantly increase SjO2 and PjO2 in comparison to isoflurane un der normoventilation, suggesting that desflurane may have stronger effect of rel axing cerebral vessel than isoflurane.

Jugular bulb oxygen saturation during desflurane and isoflurane anesthesia in pa tients undergoing brain tumor surgery / 第二军医大学学报

Objective: To investigate jugular bulb venous oxyg en partial pressure(PjO2)， hemoglobin saturation (SjO2) and the arterial t o jugular bulb venous oxygen content difference(AjDO2) during anesthesia with desflurane and isoflurane in patients with brain tumor. Methods: Fifty-six patients with brain tumor were randomized into desflur ane or isoflurane for maintaining anesthesia. PjO2, SjO2 and AjDO2 in pati ents were measured during normoventilation, hyperventilation and hypoventilation . Results: During normoventilation， SjO2 and PjO2 in desflu rane group was significantly higer than those in isoflurane group（P<0.05 or P<0.01）, and AjDO2 in desflurane group was significantly lower than that in isoflurane group（P<0.05）.Except that PjO2 in desflurane group was si gnificantly higer than that in isoflurane group during hyperventilation （P< 0.01）, there were no differences in SjO2, PjO2 or AjDO2 between the 2 g roups during hyperventilation or hypoventilation. While anesthesia with desflura ne and isoflurane, there was a positive correlation between PaCO2 and SjO2. Conclusion: At the same anesthetic effect concentration, desflur ane can significantly increase SjO2 and PjO2 in comparison to isoflurane un der normoventilation, suggesting that desflurane may have stronger effect of rel axing cerebral vessel than isoflurane.