Rifabutin loaded Inhalable β-glucan micro particle based drug delivery system for pulmonary TB

Abstract

Inhalable micro particle-based anti TB drug delivery systems are being investigated extensively for Tuberculosis [TB] treatment as they offer efficient and deep lung deposition with several advantages over conventional routes. It can reduce the drug dose, treatment duration and toxic effects and optimize the drug bioavailability. Yeast derived β-glucan is a β-[1–3/1–6] linked biocompatible polymer and used as carrier for various biomolecules. Due to presence of glucan chains, particulate glucans act as PAMP and thereby gets internalized by receptor mediated phagocytosis by phagocytes including macrophages. In this study, β-glucan microparticles were prepared by adding l-leucine as excipient, and exhibited 70% drug [Rifabutin] loading efficiency. Further, the sizing and SEM data of particles revealed a size of 2–4 µm with spherical dimensions. The FTIR and HPLC data confirmed the glucan composition of particles. The mass median aerodynamic diameter [MMAD] and Gravitational standard deviation [GSD] data indicated that these particles are inhalable in nature and have better thermal stability as per DSC thermogram. These particles were found to be non-toxic upto a concentration of 80µg/ml and are readily phagocytosed by macrophage cells in vitro as well as in vivo by alveolar macrophage. This study provides a framework for future design of inhalable β-glucan based drug carriers as a host-directed, targeted drug delivery system against Pulmonary TB.