A Novel Approach of Targeting Linezolid Nanoemulsion for the Management of Lymph Node Tuberculosis

Abstract

Tuberculosis (TB) represents a major public health problem, globally affecting children and adults. Lymphatic TB is the most common type of extrapulmonary tuberculosis, which affects the peripheral lymph nodes. This burgeoning disease requires a long-term treatment of multiple antibiotics to kill Mycobacterium tuberculosis, resulting in an increased rate of multidrug-resistant tuberculosis. To overcome drug resistance with the first-line antibiotics, linezolid W/O nanoemulsion was developed in this current work. W/O nanoemulsion was prepared by oil phase titration technique using sunflower oil, span 80 and tween 80, and optimized by pseudophase ternary diagrams. The particle size, polydispersity index, zeta potential, viscosity, and refractive index for the optimized formulation were found to be 92.32 nm, 0.066, -21.9 mV, 32.623 cP, and 1.453, respectively. Drug release from the developed nanoemulsion followed the zero-order kinetic. The antimicrobial efficacy study confirms the antibacterial potential of the developed nanoemulsion. In vivo studies conducted on Wistar rats confirms the lymphatic targeting with a high amount of drug at the target organ just after 8 h of dosing. As a result of the foregoing promising results, it may be inferred that the suggested nanoemulsion could be a viable therapy option for lymph node tuberculosis.

Figure 1

Pseudoternary phase diagram of the quaternary system containing sunflower oil, water, Span 80, and Tween 80 with span 80: Tween 80 ratio fixed at 3:1, 2:1, and 1:1.

Figure 2

Particle size distribution (a) and zeta potential (b) graph of the optimized formulation.

Figure 3

Fluorescence microscopic image of optimized formulation F-1.

Figure 4

Comparative cumulative percent drug release from nanoemulsion, capsule filled with nanoemulsion, and tablet.

Figure 5

Comparative percent microbial cell survival with control, placebo nanoemulsion, pure linezolid and linezolid nanoemulsion. (**: Statistically significant change in mean cell survival as compared to the control group, P values < 0.01 for one-way ANOVA).

Figure 6

Comparative lymphatic targeting efficiency of Linezolid to lymph node, spleen, and thymus from the encapsulated W/O nanoemulsion formulation.