ABSTRACT
The therapeutic effect of tumor photodynamic therapy is severely limited by the hypoxic tumor microenvironment. Inhibiting tumor celloxygen consumption is a more effective way than increasing its oxygen supply to overcome the tumor hypoxia and enhance photodynamic therapy. To carry out this strategy, the supramolecular nanoparticles VER-ATO-SMN loaded with photosensitizer verteporfin (VER), oxygen-consuming inhibitor atovaquone (ATO), and stabilizer polyvinylpyrrolidone (PVP)-K30 were prepared by the nanoprecipitation method, and the optimal prescription was screened and optimized by single factor experiments. The results showed that the optimal prescription for VER-ATO-SMN was ATO∶VER (w/w) = 1∶1, PVP-K30 = 100 mg, N,N-dimethylformamide∶water (v/v) = 1∶10. The morphology, particle size, particle dispersion index and encapsulation efficiency of supramolecular nanoparticles were characterized. The VER-ATO-SMN showed a spherical morphology and was well dispersed. The hydrodynamic size of VER-ATO-SMN was 101.21 ± 4.30 nm as determined by dynamic light scattering (DLS). The encapsulation efficiencies of VER and ATO in VER-ATO-SMN prepared with the optimal prescription were 70.86% and 77.52%, respectively. The VER-ATO-SMN exhibited good laser stability and also showed high stability in conditions which simulated the physiological solution. Compared with free VER and VER liposome, VER-ATO-SMN performed enhanced therapeutic effect at the cell level. The mechanism was that VER-ATO-SMN could effectively incorporate into cells and improving the intracellular oxygen concentration by reducing the oxygen consumption of tumor cells could increase the amount of reactive oxygen species generated by VER mediated photodynamic therapy. The in vivo anticancer efficacy results of tumor-bearing mice suggested that VER-ATO-SMN could effectively inhibit the tumor growth or even completely eliminate the tumor. All animal experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of 900 Hospital of the Joint Logistics Team.
ABSTRACT
Objective To assess the effects of different doses of oxycodone hydrochloride on spontaneous breathing and consciousness level of patients,so as to provide theoretical basis for its clinical application.Sixty patients undergoing elective surgery were randomly divided into 3 groups:0.05 mg · kg-1 oxycodone group (group P1),0.1 mg· kg-1 oxycodone group (group P2),0.2 mg· kg-1 oxycodone group (group P3).Changes of respiratory rate (RR),end tidal carbon dioxide partial pressure (PETCO2),saturation of blood oxygen (SpO2) and bispectral index (BIS) were recorded in patients before injection (t0) and 1-15 min after injection (once per min);the Observer's Assessment of Alertness/Sedation Scale (OAA/S) were recorded.At the same time,the adverse reactions were observed after drug injection in each group.Results In 10 min after injection there were no significant differences in the RR,SpO2,PETCO2,BIS and OAA/S in group P1 as compared with those before injection (P＞0.05).The patients had no respiratory depression in group P1.In group P2,RR had a significant decrease (P＜0.05),BIS had decreased but were greater than 85;there were no significant differences in the SpO2,PETCO2 and OAA/S (P＞0.05).The P2 group had 3 cases with respiratory frequency＜10 per min,but SpO2 were all greater than 94％.In group P3,There were significant differences in the RR,SpO2,PETCO2,BIS and OAA/S (P＜0.05).The P3 group had 12 cases of respiratory frequency ＜10 per min,at the same time there were 8 patients with SpO2 less than 94％.With the increasing dose,the frequency of respiratory inhibition increased,and there were statistical differences (P＜ 0.05).In 15 min after injection,RR,SpO2,PETCO2,BIS and OAA/S were not significantly different in group P1 and P2 as compared with those before injection (P＞0.05).In group P3,RR was significantly different after injection (P＜0.05).There were no significant differences in the SpO2,PETCO2,BIS and OAA/S in group P3 after injection (P＞0.05).No patients complained with chest wall stiffness,nausea and vomiting,cough and other adverse reactions in group P 1 and P2.In group P3,three patients had nausea 5 min after injection,two patients complained of chest skin itching but no skin flushing.Conclusion With the increasing dose,effect of oxycodone hydrochloride on breathing and consciousness level of patients gradually increased.Injection of oxycodone hydrochloride 0.05 mg · kg-1 had no obvious effect on breathing and consciousness.After injection of oxycodone hydrochloride 0.1 and 0.2 mg · kg-1 for 5 to 10 min,respiration inhibition and sedative effect were the most obvious.Fifteen min after injection,the 0.1 mg · kg-1 dose group recovered to the level before,the respiratory rate of the 0.2 mg · kg-1 dose group was still lower than that before the injection.