Construction and evaluation in vitro and in vivo of tedizolid phosphate loaded cationic liposomes

Abstract

First, the SA-TDZA-Lips were prepared by reverse-phase evaporation method. Then, the drug release behaviour was evaluated by dynamic membrane dialysis in vitro and the preliminary safety was evaluated by haemolysis method. Finally, with tedizolid phosphate injection (TDZA-Inj) and tedizolid phosphate loaded liposomes (TDZA-Lips) as the control groups, the pharmacokinetic characteristic and tissues distribution of SA-TDZA-Lips were evaluated after intravenous injection. As a result, the stearylamine modified tedizolid phosphate liposomal delivery system was constructed successfully and the particle size was 194.9 ± 2.93 nm. The encapsulation efficiency (EE) was 53.52 ± 2.18%. The in vitro release of SA-TDZA-Lips was in accordance with Weibull equation. And there was no haemolysis happened, which indicated good preliminary safety for injection. The results of pharmacokinetics showed that the t1/2β increased by 0.74 times and 0.51 times higher than that of TDZA-Inj group and TDZA-Lips group, respectively. The MRT of SA-TDZA-Lips was 1.30 and 1.09 times higher than that of TDZA-Inj group and TDZA-Lips group, respectively. The AUC was 2.40 times and 0.23 times higher than that of TDZA-Inj group and TDZA-Lips group, respectively. The tissue distribution results showed that the relative uptake rate (Re) of TDZA in the lung was 1.527, which indicated the targeting. In conclusion, the SA-TDZA-Lips prepared in this study had several advantages like positive charge, strong cell affinity, prolonged circulation time in vivo, sustained release effect, and increased drug concentration in lungs. All advantages above provided significant clinical value of application for the treatment of bacterial pneumonia with tedizolid phosphate.

Preparation and Evaluation of Stearylamine-Bearing Pemetrexed Disodium-Loaded Cationic Liposomes In Vitro and In Vivo

“…Zeta potential and EE value increased slightly with the increase of SA content. However, the increase of SA content will lead to the increase of toxicity (28). Therefore, the optimal proportion of SA was 10%.…”

“…Ultrafiltration centrifugation was devoted to assay the EE and DL of SA-PMX-Lips (28,33). For the free PMX, 100 μL of SA-PMX-Lips suspension was mixed with 200 μL distilled water into 10 kD ultrafiltration centrifuge tube and was centrifuged at 4000 rpm for 20 min (RE-52AA, Yarong, China).…”

“…Yang et al prepared chitosan-coated vancomycin hydrochloride liposomes and found that cationic liposomes evidently increase the concentration of vancomycin hydrochloride in the lung compared to the solution group (27). In another study, Yang et al adjusted the surface charge of tedizolid phosphate-loaded liposomes with stearylamine (SA) to prepare cationic liposomes, and cationic liposomes increased drug concentration in the lungs (28). SA, also known as octadecylamine, is often used to regulate the charge of liposomes.…”

“…SA interacted with the negative charges of the erythrocyte membrane and eventually damaged the cells and caused hemolysis (31). Its toxicity is positively correlated with the content of SA in liposomes (28,31). Erythrocytes from rabbit, horse, and guinea pig are highly susceptible to SA, while human erythrocytes are less sensitive to SA (30).…”

Red Blood Cell Membrane-Camouflaged Tedizolid Phosphate-Loaded PLGA Nanoparticles for Bacterial-Infection Therapy

“…Nevertheless, few studies have been performed on the novel dosage form of TR-701 in recent years. It was only loaded into 2 of 17 cationic liposomes against bacterial pneumonia, but there was a lack of pharmacodynamic studies to verify the in vivo efficacy [14]. There is actually no research on the new dosage form of TR-701 for antibacterial infection therapy.…”