RESUMO
The aim of this study was to develop a novel multifunctional nanoparticle, which encapsulates SPION and Gemcitabine in PLGA ± PEG to form multifunctional drug delivery system. For this aim, super paramagnetic iron oxide nanoparticles (SPIONs) were simultaneously synthesized and encapsulated with Gemcitabine (Gem) in PLGA ± PEG copolymers via W/O/W double emulsification method. Optimum size and encapsulation efficiency for radiosensitization, hyperthermia and diagnostic applications were considered and the preparation parameters systematically were investigated and physicochemical characteristics of optimized nanoparticle were studied. Then SPION-PLGA and PLGA-Gem nanoparticles were prepared with the same optimized parameters and the toxicity of these nanoparticles was compared with Gemcitabine in human breast cancer cell line (MCF-7). The optimum preparation parameters were obtained with Gem/polymer equal to 0.04, SPION/polymer equal to 0.8 and 1% sucrose per 20 mg of polymer. The hydrodynamic diameters of all nanoparticles were under 200 nm. Encapsulation efficiency was adjusted between 13.2% to 16.1% for Gemcitabine and 48.2% to 50.1% for SPION. In-vitro Gemcitabine release kinetics had controlled behavior. Enhancement ratios for PLGA-Gem and SPION-PLGA-Gem at concentration of nanoparticles equal to IC50 of Gemcitabine were 1.53 and 1.89 respectively. The statistical difference was significant (p-value = 0.006 for SPION-PLGA-Gem and p-value = 0.015 for PLGA-Gem compared with Gemcitabine). In conclusion, we have successfully developed a Gemcitabine loaded super paramagnetic PLGA-Iron Oxide multifunctional drag delivery system. Future work includes in-vitro and in-vivo investigation of radiosensitization and other application of these nanoparticles.
RESUMO
Objective To investigate the effects of different target plasma concentrations of propofol given by TCI on end-tidal isoflurane concentration when the depth of anesthesia was maintained at BIS 50 and evaluate the reliability of electromyography (EMG) as an anesthesia depth monitor. Methods Sixty ASA Ⅰ-Ⅱ patients aged 40-65 yrs weighing 40-85 kg undergoing elective abdominal surgery under general anesthesia were randomly allocated to one of three groups with 20 patients in each group : group Ⅰ isoflurane; group Ⅱ isoflurane + TCI propofol (1 ?g?ml-1) and group Ⅲ isoflurane + TCI propofol (2 ?g?ml-1). The patients were premedicated with intramuscular phenobarbital 0.1 g and scopolamine 0.3 mg. Anesthesia was induced with midazolam 0.05 mg?kg , fentanyl 3 ?g?kg-1 and propofol 0.5-1.0 ?g?kg-1. Tracheal intubation was facilitated with vecuronium 0.12 mg?kg-1. After intubation anesthesia was maintained with isoflurane inhalation alone (group Ⅰ) or isoflurane combined with TCI propofol at a target plasma concentration of 1 ?g?ml-1 ( group Ⅱ) or 2 ?g?ml-1 ( group Ⅲ). MAP, HR, SpO2, PETCO2, BIS, EMG and end-tidal isoflurane concentration were continuously monitored during anesthesia. BIS was maintained at 45-55 after tracheal intubation during maintenance of anesthesia.Results The three groups were comparable with respect to age, sex, body weight, duration of anesthesia and the total amount of fentanyl used during anesthesia. There were no significant differences in MAP, HR and SpO2 among the 3 groups. When BIS was maintained at 50, the end-tidal isoflurane concentration was 0.76?0.03% (group Ⅰ), 0.43? 0.08% (group Ⅱ) and 0.21?0.07% (group Ⅲ) respectively. EMG was maintained at 26-29 during operation. During emergence from anesthesia EMG value increased with BIS value. When the patients opened their eyes at command EMG value was about 40. The correlation between BIS and EMG was poor. Conclusion At the samedepth of anesthesia (BIS = 50) the end-tidal isoflurane concentration was greatly reduced when combined with TCI propofol. EMG value decreases with increasing depth of anesthesia but as an anesthesia depth monitor it still needs improving.