Radiolabeled Tedizolid Phosphate Liposomes for Topical Application: Design, Characterization, and Evaluation of Cellular Binding Capacity

AAPS PharmSciTech. 2021 Feb 2;22(2):62. doi: 10.1208/s12249-020-01917-4.


Nowadays, the incidence of acute bacterial skin and skin structure infection (ABSSSI) is increasing. The increased bioavailability and reduced drug resistance of antibiotics are crucial to obtain a more effective treatment response in these infections. These favorable properties could be achieved by different drug delivery systems such as liposomes. In this study, nanosized, radiolabeled tedizolid phosphate liposomal formulations were prepared and evaluated with their in vitro cellular binding capacity and biocompatible profile for topical treatment of ABSSSI. Liposomes were characterized by evaluation of their visual inspection, particle size (about 190-270 nm), zeta potential value (around 0), and encapsulation efficiency (nearly 10%). The release rate of tedizolid phosphate from liposomes was also studied using dialysis membranes and evaluated kinetically. The stability of formulations was observed at three different temperatures and humidity conditions for 28 days. Afterward, liposomes were labeled with 99mTc, and the optimal amount of reducing agent (stannous chloride) was determined as 500 μg in this direct labeling procedure. All liposome formulations were successfully radiolabeled with high efficiency and exhibited high radiochemical purity (> 80%) during 6 h in different media. Furthermore, the cellular bindings of liposomal formulations were evaluated in human skin fibroblast cells by measuring the radioactivity. Higher radioactivity values were obtained in CCD-1070Sk cells incubated by liposome formulations compared to sodium pertechnetate. This finding suggested that liposomal formulation increased the cellular binding of radioactivity. By the result of our study, nanosized, tedizolid phosphate encapsulated liposome formulation was found to be a favorable carrier system in the treatment of ABSSSI.

PMID:33528714 | DOI:10.1208/s12249-020-01917-4