Aerosolized Vesicular Drug Delivery Systems Targeting the Respiratory Tract

Abstract

Tuberculosis (TB) is a severe respiratory infectious disease, induced by intracellular microorganism called mycobacterium tuberculosis. About one third of world population is infected with TB but actually only 10% of infected individuals develop active disease. The incidence rate of active TB increases with increasing the number of immunocomporomized patients associated with increase in the number HIV patients, patients undergone organ transplantation, patients receiving chemotherapy for treatment of cancer. About 80% of TB infections are pulmonary tuberculosis in which the mycobacteria reside and proliferate in alveolar macrophages and resist their killing mechanisms. Moxifloxacin hydrochloride has potent activity against mycobacterium tuberculosis. Being a fourth generation fluoroquinolones, it inhibits DNA gyrase and topoisomerase IV, responsible for unfolding of DNA, so inhibits bacterial DNA replication leading to bacterial death. Although most anti-mycobacterial drugs have interactions with antiretroviral drugs but MXF does not have any reported interactions with them so simultaneous therapy is possible and effective. In this thesis, our aim is to treat pulmonary tuberculosis by local pulmonary delivery using dry powder inhaler. These will ensure high local MXF concentration, decrease the frequency of administration with an expected reduction in the required dose and hence side effects. The MMAD is the key parameter controlling the site of deposition of the dry powder in the respiratory tract, where particles <1µm move by Brownian motion and are usually exhaled, particles > 5µm deposit in the oropharynx, while particles of MMAD between 1-5µm deposit in the lower respiratory tract and deep alveoli by sedimentation. In addition we aim to load MXF in liposomes which constitute of biodegradable, biocompatible and non-immunogenic phospholipid. Being spherical structure of phospholipid so liposome can be easily phagocytized by alveolar macrophages and enhance drug delivery to mycobacterial cells