Morphological transition of M. tuberculosis and modulation of intestinal permeation by food grade cationic nanoemulsion: In vitro-ex vivo-in silico GastroPlus™ studies

Abstract

The study aimed to investigate rifampicin (RIF) loaded cationic nanoemulsion (NE) for increased efficacy, facilitated intestinal permeability and GastroPlus™ based prediction. Formulations were prepared and characterized for robustness to dilution, cloud point and stability to varied pH. Morphological transition of M. tuberculosis H37 Rv was studied by a transmission electron microscopy (TEM), % inhibition study and cytoplasmic content analysis. The ex vivo permeation and confocal laser scanning microscopy (CLSM) studies were conducted using duodenum, jejunum and ileum. Results of robustness ensured stability to dilution, pH and temperature (˃ 37 °C). The Smix (surfactant to co-surfactant) ratio (2:1 and 3:1) possessed maximized % inhibition due to LAB and AC8. The Peff values of cationic NE were 2.25, 1.96 and 2.0 fold higher than DS (drug solution) for duodenum, jejunum and ileum, respectively, whereas enhancement ratios were 2.25-, 1.94- and 2.0 fold higher than DS. A CLSM showed 3.22-, 2.89-, and 1.1 fold higher % fluorescence intensity from duodenum, jejunum and ileum, respectively. GastroPlus™ predicted 100% regional absorption of RIF-cationic NE and considerable effect of globular size, permeability and nanonization on pharmacokinetics (PK) parameters. Conclusively, the cationic NE can be a promising approach for increased efficacy of RIF and augmented oral absorption to control tuberculosis.