Inhalable dry powders for pulmonary vaccination

Abstract

The present thesis includes two parts. The first part of the work was focused on the design, development and characterisation of a formulation to deliver a novel antigen against human papillomavirus (HPV) by inhalation. Pulmonary delivery represents an attractive alternative route of administration for vaccines: it is needle-free, noninvasive and that does not require “cold chain”. In specific, the goal was to design a highly respirable dry powder produced by spray drying, through a particle engineering approach of molecular deposition of amphiphilic molecules. The produced powders showed in vitro respirability higher than 70%, and preferential deposition in the lungs in vivo as well as significant immune response. The second part of the project was devoted to the development of a novel platform for pulmonary administration of two first-line antimycobacterial drugs with specific targeting to alveolar macrophages (AMs) to be used in the treatment of mycobacterial infections. The specific aim of this section was to produce and characterize an innovative dry powder for inhalation (DPI) in the form of highly respirable microparticles consisting of nanoparticle agglomerates targeting AMs phagocytosis. The particles were loaded with two antibiotics, namely rifampicin and isoniazid, and one efflux pump inhibitors, verapamil hydrochloride. In this case too, the produced powder afforded high in vitro reparability, adequate de-aggregation and dissolution rate and proved to be affective for AMs engulfment as well as to inhibit mycobacterial growth.