Cationic rifampicin nanoemulsion for the treatment of ocular tuberculosis

Abstract

Ocular infection caused by Mycobacterium tuberculosis affected an estimated 0.1−0.2 million people in the year 2018 worldwide and may result in irreversible loss of vision if not treated properly. Despite this significant figure, the only therapy used to date is the oral administration of anti-tuberculosis drugs substances, mainly rifampicin (Rif), which presents severe adverse effects. Besides, the blood-retinal barrier (BRB) impairs the drug substance bioavailability into the eye. Thus, it is needed urgently an ophthalmic preparation to treat this infection. Cationic nanoemulsion (NE) has been considered a major shift towards an effective ophthalmic drug delivery. To the best of our knowledge, our study presents the first ophthalmic cationic nanoemulsion for the treatment of ocular tuberculosis. In our study, a Rif-loaded cationic nanoemulsion with specific surface modification employing chitosan (CS) and polymyxin B (PB) was developed successfully. Rif-NE + CS and Rif-NE + PB preparations exhibited particle size of approximately 150 nm, and zeta potential values of +51.3 mV and +5.5 mV, respectively. in vitro assessment of mucoadhesion test indicated electrostatic interaction of cationic nanoemulsions with negative charged mucin, which may improve the preparation efficacy by increasing its residence time on the organ of vision. In vitro antimicrobial activity showed that the high-pressure homogenization (HPH) method and surface modification process did not affect the antimicrobial efficacy of Rif. These findings may enable a promising alternative line of ophthalmic products for the management of ocular tuberculosis with potential longer interval between administration.