Research Projects

Tuberculosis is a leading infectious disease in India, with treatment challenges including poor drug targeting, lengthy regimens, systemic side effects, and emerging drug resistance. Efficient delivery of anti-TB drugs directly to infected lung macrophages within granulomas could significantly improve therapeutic outcomes. This project aims to develop inhalable polyelectrolyte complex (PEC) microparticles using sulphated locust bean gum (SLBG) and chitosan to encapsulate first-line anti-TB drug like Ethambutol. SLBG’s mannose-rich structure is exploited for receptor-mediated targeting of CD206+ macrophages, which are upregulated during Mycobacterium tuberculosis infection. Beyond drug delivery, the SLBG chitosan PEC matrix may also exhibit intrinsic antibacterial activity, particularly owing to chitosan’s ability to disrupt bacterial cell membranes and the immunomodulatory potential of sulphated polysaccharides, offering a dual-action approach against Mycobacterium tuberculosis. The study involves optimizing formulation parameters to enhance drug loading, stability, and controlled release. Uptake and targeting efficiency will be evaluated in M.tuberculosis -infected THP-1-derived and primary human monocyte-derived macrophages expressing CD206. Detailed physicochemical and aerosol characterization will include particle size, surface charge, morphology, encapsulation efficiency, drug release kinetics, and aerosol performance (MMAD, FPF). Therapeutic efficacy will be evaluated using a 3D collagen-based TB infection culture system developed from macrophages infected with M. tuberculosis, which replicates key features of the infected microenvironment and better simulates in vivo-like conditions. Assessments will include particle uptake, drug penetration, bacterial clearance (via CFU assay), and immunomodulatory responses (via cytokine profiling and confocal microscopy. Findings will guide the subsequent in vivo evaluation in a murine TB model, enabling better prediction of lung targeting, therapeutic outcomes, and biosafety after pulmonary administration. The expected outcome is a biocompatible, effective inhalable formulation that improves drug delivery to lung macrophages, enhancing bacterial clearance and reducing systemic toxicity. This project addresses a significant national health challenge by developing innovative, targeted TB treatment with potential for clinical translation. My research background in developing multifunctional biomaterials and polymer-based nanocomposites for antimicrobial and therapeutic applications provides a strong foundation for engineering advanced drug delivery systems in this context. The project will be guided by Prof. Rachit Agarwal (Dept. Of Bioengineering, IISc Bangalore) whose expertise in biomaterials, tuberculosis models particularly 3D TB culture systems and macrophage-targeted drug delivery ensures strong alignment with the proposed work and supports its successful execution.