Lipid-Based Nano Formulation Approach to Target Brain for the Management of Tuberculosis through Intranasal Delivery: Formulation Development and Evaluation

Objectives: Development of nano-emulsion based drug delivery as combined drug loaded form for the possible management of meningitis. Intranasal delivery of nano-emulsion to the brain and study the nasal irritancy. Methodology: Spontaneous emulsification method was used in preparing the nanoemulsion. The compatibility studies i.e., Differential Scanning Colorimetry and Fourier Transform Infrared Spectroscopy were carried out for Isoniazid, Rifampicin, Resveratrol and physical mixture. Pseudoternary phase diagrams were constructed in various ratios. The formulations which passed the thermodynamic stability studies were evaluated for particle size, zeta potential and poly dispersity index. Cytotoxicity of the pure drugs and formulations were measured in in vitro cell line. The formulations were given for histopathological studies. Then these formulations were administered to rats intranasally and the brain of the rats was collected. Then the brain tissue was minced and was given for LCMS analysis to know the amount of drug reaching the brain. Results: The DSC and FTIR graphs state that the drugs were compatible with each other. The formulations which passed the thermodynamic stability studies were A7, A9, J8 and G9. Among these formulations A7 was selected as it had lower particle size when compared to other formulations. The formulations showed low nasal irritancy and no malignancy. From the LCMS analysis it was found that 82.6% of Isoniazid with Resveratrol nanoemulsion and 78.48% of Rifampicin with Resveratrol nanoemulsion has reached the targeted area the brain. Conclusion: From the studies it can be concluded that when the formulations were administered intranasally maximum amount of the drugs had reached the targeted area the brain. So, when the drugs are given intranasally there could be decrease in the dose of the drug, increased bioavailability at the site of action and increased therapeutic efficacy.