Targeted theranostic liposomes: rifampicin and ofloxacin loaded pegylated liposomes for theranostic application in mycobacterial infections

Abstract

Theranostic liposomes are effective drug delivery systems for the management of infections. With added features of targeting and stealth, theranostic liposomes can be made more effective. We report the synthesis and validation of targeted stealth theranostic liposomes for the management of mycobacterial infections. The targeted drug delivery systems for infections are devised to improve the therapeutic window of encapsulated drugs by increasing their delivery to the target area and minimizing the drug-associated toxicity. FR+ targeted pegylated liposomal formulation was developed for in vivo imaging of mycobacterial infections. The encapsulated drugs for mitigation are rifampicin and ofloxacin. The prepared liposomes were characterized for physicochemical properties and stability. In vitro release properties, mycobacterial activity, in vivo blood-kinetics, bio-distribution, and bio-efficacy of the prepared lyophilized liposomes were assessed. The mean particle size of the liposomes was 160.6 nm with considerable colloidal stability observed up to 120 days. The results of in vitro investigations indicate good encapsulation efficiency of 66.89 (±10.9)% and 40.61 (±8.7)% for rifampicin and ofloxacin respectively with excellent anti-mycobacterial activity. The pharmacokinetics data corroborate a slow biphasic pattern with a much longer terminal half-life of 19.13 h. The tissue distribution studies revealed high blood pool activity even up to 24 h post injection (p.i.) with the maximum organ localization in the spleen, liver, and kidneys at one hour p.i. Further, in vivo scintigraphic studies in the murine model of TB infection showed higher uptake at infected lesions at two hours p.i. The blocking imaging experiments showed minimized uptake, which confirms specific targeting. Therapeutic efficacy studies further confirmed that liposomal delivery of the anti-TB drugs is efficacious in the murine model of infection. In conclusion, preliminary studies demonstrated that the formulated liposomes can be an effective theranostic agent against mycobacterial infections in the mouse model.