Pulmonary drug delivery by powder aerosols

Yang, Michael Y.; Chan, John Gar Yan; Chan, Hak‐Kim

doi:10.1016/j.jconrel.2014.04.055

Cited by 161 publications

(78 citation statements)

References 159 publications

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“…This leads to an increase of the internal pressure that might reach a critical point where the particle deforms or even disintegrates [21]. The irregular morphology observed in the microparticles of this work may improve the dispersibility and flow properties of dry powders, as surface irregularities will reduce the contact between microparticles and the possibility of establishing van der Waals forces that lead to agglomeration [22]. It is important to highlight that, from an eye observation, the presence of RFB in microparticles seemed to improve dispersibility, an effect that was concentration-dependent, as it was particularly visible for formulations LBG:RFB = 10:1 and 10:0.5 (w/w).…”

Section: Association Of Drugs and Characterisation Of Microparticlesmentioning

confidence: 88%

Inhalable Antitubercular Therapy Mediated by Locust Bean Gum Microparticles

et al. 2016

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Tuberculosis remains a major global health problem and alternative therapeutic approaches are needed. Considering the high prevalence of lung tuberculosis (80% of cases), the pulmonary delivery of antitubercular drugs in a carrier system capable of reaching the alveoli, being recognised and phagocytosed by alveolar macrophages (mycobacterium hosts), would be a significant improvement to current oral drug regimens. Locust bean gum (LBG) is a polysaccharide composed of galactose and mannose residues, which may favour specific recognition by macrophages and potentiate phagocytosis. LBG microparticles produced by spray-drying are reported herein for the first time, incorporating either isoniazid or rifabutin, first-line antitubercular drugs (association efficiencies >82%). Microparticles have adequate theoretical properties for deep lung delivery (aerodynamic diameters between 1.15 and 1.67 µm). The cytotoxic evaluation in lung epithelial cells (A549 cells) and macrophages (THP-1 cells) revealed a toxic effect from rifabutin-loaded microparticles at the highest concentrations, but we may consider that these were very high comparing with in vivo conditions. LBG microparticles further evidenced strong ability to be captured by macrophages (percentage of phagocytosis >94%). Overall, the obtained data indicated the potential of the proposed system for tuberculosis therapy.

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Section: Association Of Drugs and Characterisation Of Microparticlesmentioning

confidence: 88%

Inhalable Antitubercular Therapy Mediated by Locust Bean Gum Microparticles

et al. 2016

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“…The mechanisms of particle agglomeration, as summarized by Schneider and Jensen (2009), include physical interlock (rough surface, entangled surface shapes, or chain-like, branched structure), electric forces (Van der Waal, conductive/non-conductive), magnetic forces (ferromagnetic, induced magnetic) and soft bridging (sticky surface, liquid film, organic functional groups). Previous studies reported that the deagglomeration of such submicron clusters is dependent on the energy present in the process from which they are released and the turbulence of their transport in the air (Islam & Cleary, 2012;Yang, Chan, & Chan, 2014). Such processes have also been shown to release primary particles or smaller, nano-sized agglomerates (Froeschke, Kohler, Weber, & Kasper, 2003;Stahlmecke et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

A system to assess the stability of airborne nanoparticle agglomerates under aerodynamic shear

Ding

Riediker

2015

Journal of Aerosol Science

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a b s t r a c tStability of airborne nanoparticle agglomerates is important for occupational exposure and risk assessment in determining particle size distribution of nanomaterials. In this study, we developed an integrated method to test the stability of aerosols created using different types of nanomaterials. An aerosolization method, that resembles an industrial fluidized bed process, was used to aerosolize dry nanopowders. We produced aerosols with stable particle number concentrations and size distributions, which was important for the characterization of the aerosols' properties. Next, in order to test their potential for deagglomeration, a critical orifice was used to apply a range of shear forces to them. The mean particle size of tested aerosols became smaller, whereas the total number of particles generated grew. The fraction of particles in the lower size range increased, and the fraction in the upper size range decreased. The reproducibility and repeatability of the results were good. Transmission electron microscopy imaging showed that most of the nanoparticles were still agglomerated after passing through the orifice. However, primary particle geometry was very different. These results are encouraging for the use of our system for routine tests of the deagglomeration potential of nanomaterials. Furthermore, the particle concentrations and small quantities of raw materials used suggested that our system might also be able to serve as an alternative method to test dustiness in existing processes.

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“…Supercritical fluid technology is another bottom-up technology that generates uniformly sized particles for pulmonary delivery (Sacchetti and Van Oort, 2007). For reviews on dry powder formulation for pulmonary delivery, the readers are directed to articles that broadly cover these topics (Yang, Chan and Chan, 2014;Carvalho et al, 2015;Hickey, 2018).…”

Section: Formulation Innovationsmentioning

confidence: 99%

Challenges Associated with the Pulmonary Delivery of Therapeutic Dry Powders for Preclinical Testing

Price

Kunda

Muttil

2019

KONA

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Significant progress has been made over the last half-century in delivering therapeutics by the pulmonary route. Inhaled therapeutics are administered to humans using metered-dose inhalers, nebulizers, or dry powder inhalers, and each device requires a different formulation strategy for the therapeutic to be successfully delivered into the lung. In recent years, there has been a shift to the use of dry powder inhalers due to advantages in the consistency of the dose delivered, ease of administration, and formulation stability. Numerous preclinical studies, involving small and large animals, have evaluated dry powder drugs, vaccines, and immunotherapeutics delivered by the pulmonary route. These studies used different dry powder delivery devices including nose-only, whole-body, and intratracheal administration systems, each of which works with different aerosolization mechanisms. Unfortunately, these delivery platforms usually lead to variable powder deposition in the respiratory tract of animals. In this review, we will discuss obstacles and variables that affect successful pulmonary delivery and uniform powder deposition in the respiratory tract, such as the type of delivery device, dry powder formulation, and the animal model used. We will conclude by outlining factors that enhance the reproducible deposition of dry powders in the respiratory tract of preclinical animal models and identifying knowledge and technology gaps within the field. We will also outline the important factors necessary for successful translation of studies performed in preclinical models to humans.

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Pulmonary drug delivery by powder aerosols

Cited by 161 publications

References 159 publications

Inhalable Antitubercular Therapy Mediated by Locust Bean Gum Microparticles

Inhalable Antitubercular Therapy Mediated by Locust Bean Gum Microparticles

A system to assess the stability of airborne nanoparticle agglomerates under aerodynamic shear

Challenges Associated with the Pulmonary Delivery of Therapeutic Dry Powders for Preclinical Testing

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