In vivo efficacy and pharmacokinetics of bi-aryl oxazolidinone RBx 11,760 loaded polylactic acid–polyethylene glycol nanoparticles in mouse hematogenous bronchopneumonia and rat groin abscess caused by Staphylococcus aureus ☆

Tarani Kanta Barman, Manoj Kumar, Tridib Chaira, Manu Dalela, Dikshi Gupta, Paras Kumar Jha, Ajay Singh Yadav, Dilip J. Upadhyay, V Samuel Raj, Harpal Singh

Index: 10.1016/j.nano.2018.02.003

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Abstract

RBx 11,760 is a bi-aryl oxazolidinone antibacterial agent active against Staphylococcus aureus but has poor solubility. Here we have encapsulated RBx 11,760 in PLA–PEG NPs with an aim to improve physicochemical, pharmacokinetics and in vivo efficacy. The average size and zeta potential of RBx 11,760 loaded NPs were found to be 106.4 nm and −22.2 mV, respectively. The absolute size of nanoparticles by HRTEM was found to be approximately 80 nm. In vitro antibacterial agar well diffusion assay showed clear zone of inhibition of bacterial growth. In pharmacokinetic study, nanoparticle showed 4.6-fold and 7-fold increase in AUCinf and half-life, respectively, as compared to free drug. RBx 11,760 nanoparticle significantly reduced bacterial counts in lungs and improved the survival rate of immunocompromised mice as compared to free drugs. Thus, RBx 11,760 loaded nanoparticles have strong potential to be used as nanomedicine against sensitive and drug resistant Staphylococcus aureus infections.