# Sustained Delivery of Rifampicin Nanoformulation Administration Intravitreally Into Rabbit Eyes for Ocular Tuberculosis

## TL;DR

Researchers developed a nanoformulation of rifampicin that can be injected into the eye to provide sustained drug release for treating ocular tuberculosis.

## Contribution

A novel sustained-release rifampicin nanoformulation was developed for intravitreal administration to treat ocular tuberculosis.

## Key findings

- Rifampicin-loaded PLGA nanoparticles sustained drug levels in the vitreous for seven days compared to one day for free rifampicin.
- The nanoformulation achieved higher peak concentrations and did not enter systemic circulation.
- The nanoparticles had an encapsulation efficiency of 67.68% and a loading capacity of 42.28%.

## Abstract

Introduction: Diagnosis and treatment of ocular tuberculosis is very challenging. It poses a significant and potential management dilemma after diagnosis as a primary, active, or secondary infection. The higher amounts of orally administered antitubercular drugs are needed to achieve the therapeutic concentration in the eye, which may lead to a higher risk of side effects. However, the intravitreal administration of drugs is not practiced because of the frequent administration of the injections.

Methods: This study was carried out to develop, optimize, and characterize rifampicin-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles to make them sustained release followed by the direct administration of plain rifampicin and rifampicin nano-formulations in the vitreous of rabbit eyes. Both groups were comparatively assessed for the sustained delivery of the two preparations in the vitreous and their systemic toxicity.

Results: The characteristics of rifampicin-loaded nanoparticles were 786 nm in size with narrow size distribution along with a zeta potential of -12 mV. The drug encapsulation efficiency and loading capacity were 67.68% w/w and 42.28% w/w, respectively. The four New Zealand white rabbits were divided into two groups and given plain rifampicin (50µl volume) and PLGA nanoformulations of rifampicin (50µl volume) in each eye. In vivo, rifampicin-loaded PLGA nanoparticles produced sustained release of rifampicin for a week, even obtaining the 0.51 µg/ml levels on the seventh day in vitreous against negligible levels after one day for free rifampicin. The Cmax levels for free Rifampicin and Rifampicin nanoparticles were 0.44 µg/ml and 1.86 µg/ml, respectively.

Conclusion: In this experimental proof-of-concept study, we have found that rifampicin-loaded PLGA nanoparticles released rifampicin in a sustained manner for up to seven days compared to free drugs only for one day into the vitreous. The intravitreal-administered drug did not reach systemic circulation.