The role of particle physico-chemical properties in pulmonary drug delivery for tuberculosis therapy

Abstract

There is increasing interest in the use of inhaled aerosol drug therapy for the treatment of tuberculosis (TB). A number of methods of preparation of particles have been employed including spray drying, solvent evaporation, emulsion and phospholipid methods to create microparticles, macroaggregated nanoparticles, solid lipid nanoparticles and liposomes. Each of these methods involves the use of different proportions of additives to aid in the particle formation or to achieve important physico-chemical properties such as ease of dispersion. While these approaches all have merit their practical value is limited by constraints on dose and means of delivery as an aerosol in order to achieve a therapeutic effect. A review of a number of approaches is presented and placed in the context of the need for effective aerosol delivery systems for the treatment of TB as a guide to selection of appropriate excipients, processes and delivery strategies to support product development activities.

An Inhalable Theranostic System for Local Tuberculosis Treatment Containing an Isoniazid Loaded Metal Organic Framework Fe-MIL-101-NH2—From Raw MOF to Drug Delivery System

“…In fact, the use of excipients in pulmonary drug delivery, albeit necessary to provide the required aerodynamic and rheological properties, can be a considerable pitfall for inhaled antibiotic therapies, since it can determine the need for an excessive aerosolized mass of material to reach the required effective dose. Whether the goal is targeting pathogen's niches or grant local and systemic therapeutic levels, a high drug concentration and low amount of excipient are desirable, because the quantity of material that the patient is able to inhale without adverse events sets the size of the therapeutic window [53]. Naturally, if the aim of the therapy is to target macrophages, the excipients should provide a slower dissolution rate, for prolonged internalization by phagocytosis [33].…”

Glucosamine/L-lactide copolymers as potential carriers for the development of a sustained rifampicin release system using Mycobacterium smegmatis as a tuberculosis model

“…3, insets). The size and shape of the particles are crucial factors for delivery into the pulmonary airways: particles with aerodynamic diameters between 1-5 μm are preferred (Mohamed & Van Der Walle, 2008; Mortensen et al., 2014). MP with sizes larger than 5 μm are usually deposited in the oral cavity, and SMP particles smaller than <0.5 μm move by Brownian motion and settle slowly.…”

Exploring inhalable polymeric dry powders for anti-tuberculosis drug delivery

“…Particles with an aerodynamic diameter in the range 1-5 μm are deposited in the lower airways, which is a desirable location for anti-TB drugs [13,[26][27][28]. On the other hand, particles larger than 5 μm undergo deposition in the upper regions, such as the nasopharynx and they are consequently swallowed, while particles smaller than 1 μm are likely to be exhaled or retained in the alveoli if transported by a carrier system [13,26,29]. After reaching the lower airways, particulate systems are likely to be either phagocytized by alveolar macrophages, adhere to the lung tissue or enter the blood circulation via lung vascular tree.…”