The poor bioavailability of chemotherapeutic drugs, such as methotrexate (MTX), plays a critical role in their success. Solid lipid nanoparticles (SLNs) have emerged as vital therapeutic carriers owing to the biocompatible nature of their constituent materials. In this study, a nanoparticulate system, consisting of a pegylated lipid core of stearic acid, has been designed to evaluate its potential for encapsulation and delivery of the chemotherapeutic drug MTX, which often suffers from poor bioavailability. Stable pegylated SLN formulations of MTX having a mean particle size ~130 nm (zeta potential −34 mV) and low polydispersity were prepared and completely characterized using DSC, TEM and AFM. They were found to present an almost spherical morphology. These drug-loaded formulations were found to have good hemocompatibility, as quantified by hemolysis analysis. In vitro drug release studies at acidic pH (5.5) and physiological pH (7.4) revealed a power-law mechanism of release of MTX from the SLNs. These MTX-loaded formulations have been evaluated biologically with the help of radiolabeling techniques (with ^99mTc radionuclide). The blood kinetics profile of the ^99mTc radiolabeled pegylated MTX formulations in New Zealand Albino rabbits revealed higher blood circulation times, while the biodistribution studies in tumour models (balb/c mice) revealed their efficient tumour uptake, as evidenced by SPECT imaging. These studies convey the potential use of these pegylated SLNs based on stearic acid for improving the bioavailability of MTX and they can be expected to be a valuable addition to the array of nanoparticles with potential therapeutic applications.

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.