In spite of many advantages of vesicular systems through pulmonary route, its use is limited because of significant complications for drug delivery such as aggregation, increased size of the vesicles by fusion of vesicles during storage, sedimentation, leakage of encapsulated drug, hydrolysis and oxidation of components of the formulation during storage. However, these stability problems can be avoided by formulating them as provesicular systems i.e proliposomal and proniosomal powders, a novel approach which produces vesicles in situ upon contact with biological fluids (Betageri 2005; Payne et al., 1986).
Provesicular powder is a dry free-flowing powder, produces vesicles upon hydration with water or biological fluids (Payne et al., 1986) and avoids the stability problems associated with vesicles.
Significance of provesicular systems
Improves the stability of vesicular systems.
Acts as drug reservoirs and the rate of drug release can be controlled by modification of their composition (Chandra et al., 2008).
Drug targeting can be achieved.
They possess additional convenience of combining the advantages of vesicular systems with that of solid dosage forms that involve ease in transportation, processing, storage, and accurate dosing (Hu and Rhodes, 2000).
They retain the integrity of vesicles at the site of absorption by forming vesicles only at the site of delivery.
The present study aimed to develop stable provesicular dry powder formulations for pulmonary delivery to treat MDR-TB by entrapping first line anti- tubercular drug along with second line drug with different solubilities.
The main objective of the present study is to develop novel noninvasive pulmonary delivery of anti-tubercular drugs for improved therapy. The developed provesicular system undergoes hydration with biological fluid and produces vesicles after administration by pulmonary route. Then these vesicles would be internalized by alveolar macrophages through endocytosis and presented to lysosome or escaped from endosome and releases drugs intracellularly. The drugs released form the vesicles reaches the latent bacilli and shows action (Shown in Figure 2). This strategy would increase high drug concentration at target site and improve the therapeutic action of drugs which would help in shortening the duration of tuberculosis therapy clinically.
Specifically the proposal would aim in developing and exploring the efficiency of novel provesicular based dry powder pulmonary delivery system as single dose inhalation therapy for two antitubercular drugs to deliver alveolar macrophages and eradicating persister’s population as well and avoiding drug resistance.
Aims of the project
The principal aim of this study is to explore the potential of provesicular based dry powder systems for pulmonary delivery of two anti-tubercular drugs at once to treat MDR-TB.
To develop provesicular dry powder system containing fixed dose combinations of antitubercular...