ABSTRACT
Objective To prepare F7 thermosensitive liposome and evaluate its physicochemical properties, then investigate its cytotoxicity against tumor cells in vitro. Methods The F7 thermosensitive liposome was prepared by the pH gradient active drug loading method using dipalmitoyl phosphatidylcholine myristoyl lyso-phosphocholine and 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy (polyethylene glycol)-2000 as membrane materials. The encapsulation efficiency and drug loading were determined for the F7 thermosensitive liposome by HPLC. The phase transition temperature of F7 thermosensitive liposome was investigated by differential scanning calorimetry;the liposome morphology was observed by atomic force microscopy;the drug release of liposome was examined by dialysis;and the particle size and zeta potential were measured through Malvern particle size analyzer. The cytotoxicity of F7 and F7 thermosensitive liposome was determined by the MTT method, and the freeze-drying process was optimized using the designexpert software. Results The encapsulation efficiency of F7 thermosensitive liposomes was (97.56±0.22) ％, and the drug loading ratio was (1.51±0.01) ％. The phase transition temperature of F7 thermosensitive liposome was 39.9℃, the zeta potential was (-15.10±0.85) mV, the particle size was (86.94±1.21) nm, and the poly disperse coefficient was 0.17±0.01. Compared with the F7 injection, the F7 thermosensitive liposomes showed a stronger, dose-dependent inhibitory effect on the growth of lung cancer H1299 and breast cancer MCF-7 cells. The freeze-dried powder of liposomes dissolved well with the encapsulation efficiency of 95％ and the particle size of approximately 130 nm. Conclusion The F7 thermosensitive liposome prepared by the pH gradient active drug loading method has high encapsulation efficiency and good stability. The preparation method is simple and feasible for further development of the F7 preparation.
ABSTRACT
Objective: To establish and validate a LC-MS/MS method for quantitative analysis of a new anti-stroke compound TID-101 in rat plasma and to study the pharmacokinetics and bioavailability of TID-101 self-(micro)emulsified drug delivery system(SMEDDS). Methods: The plasma samples were treated with methanol for precipitating protein. The chromatographic separation was achieved with a acetonitrile-water mobile phase. Detection of TID-101 and the internal standard (IS) dexamethasone acetate was achieved by electrospray ionization (ESI) source in the negative ion mode at m/z 353.4→323.2 and m/z 433.4→353.4. The method was applied for pharmacokinetics study of TID-101 between SMEDDS in rats. Results: The method was linear over TID-101 concentration range from 10-95 000 ng/ml with the correlation coefficients (r) of 0.9998. The intra-run and inter-run relative standard deviations(RSD) were less than 15% and the average absolute recovery values were 83.4-87.0%. The validated method was applied to a pharmacokinetic study in rats after intravenous administration of TID-101 fat emulsion injection and oral administration of TID-101 suspension and SMEDDS. The bioavailability of TID-101 API and SMEDDS was 2.8% and 14.9%, respectively. Conclusion: The analysis method is simple, accurate, and sensitive for assaying the in vivo pharmacokinetic study of TID-101 in rats. SMEDDS could effectively enhance the oral bioavailability of TID-101.
ABSTRACT
Nowadays, nanotechnologies have shown wide application foreground in the biomedical field of medicine laboratory tests, drug delivery, gene therapy and bioremediation. However, in recent years, nanomaterials have been labeled poisonous, because of the disputes and misunderstandings of mainstream views on their safety. Besides, for the barriers of technical issues in preparation like: (1) low efficacy (poor PK & PD and low drug loading), (2) high cost (irreproducibility and difficulty in scale up), little of that research has been successfully translated into commercial products. Currently, along with the new theory of "physical damage is the origin of nanotoxicity", biodegradability and biocompatibility of nanomaterials are listed as the basic principle of safe application of nanomaterials. Combining scientific design based on molecular level with precision control of process engineering will provide a new strategy to overcome the core technical challenges. New turning point of translational medicine in nanotechnology may emerge.