Packaging and Delivery of Asthma Therapeutics

Abstract

Asthma is a life-altering, chronic disease of heterogenous origin that features a complex interplay of immune and environmental signaling. Although very little progress has been made in prevention, diverse types of medications and delivery systems, including nanoscale systems, have been or are currently being developed to control airway inflammation and prevent exacerbations and fibrosis. These medications are delivered through mechanical methods, with various inhalers (with benefits and drawbacks) existing, and new types offering some variety in delivery. Of particular interest is the progress being made in nanosized materials for efficient penetration into the epithelial mucus layer and delivery into the deepest parts of the lungs. Liposomes, nanoparticles, and extracellular vesicles, both natural and synthetic, have been explored in animal models of asthma and have produced promising results. This review will summarize and synthesize the latest developments in both macro-(inhaler) and micro-sized delivery systems for the purpose of treating asthma patients.

Keywords: asthma; drug packaging; exosome; inhaled medications; liposome; nanoparticle.

Figure 3

Modes of Action. Specificity for checkpoints in the asthma pathway is the hallmark of an effective therapy. (A) Inhaled corticosteroids [47,48], (B) theophylline [51,52], (C) long-acting beta agonists [57], (D) leukotriene receptor antagonists [62], (E) monoclonal antibodies [66,67,68], and (F) anti-histamines [71,72] offer diverse targeting specific to halting airway inflammation. Created in BioRender.com.

Figure 1

Sources and Pathway of Asthmatic Exacerbations. Dust, pollen, pet dander, and smoke from cigarettes or other sources are potent asthmatic triggers [16,17]. Created in BioRender.com.

Figure 2

Multi-Phase Drug Metabolism in Hepatocytes. Distinct phases of drug metabolism that increase polarity through enzymes that modify xenobiotics via addition of functional groups are crucial for excretion of ingested medications [25,28,29,32]. Created in BioRender.com.

Figure 4

Customized Delivery Systems. Liposomes (left), nanoparticles (center), and exosomes (right) can be tailored to penetrate into the deepest parts of the lung and deliver therapeutics directly to epithelial cells through the mucus layer. Created in BioRender.com.

Figure 5

New Horizons in Delivery Potential. Microscale structures can be engineered to (A) carry nanoscale particles deep into the lungs and past the mucous barrier, (B) release enzymes to locally modify the mucous for easier penetration of subsequent medicines, or (C) release gene therapy materials to change mucous expression profiles. Created in BioRender.com.

Figure 6

Asthma-COPD Overlap Syndrome (ACOS). Chronic obstructive pulmonary disorder (left) is primarily IL-8/neutrophil mediated while asthma (center) is IL-4/5/13 and T-cell mediated ACOS (right) features symptoms from both diseases and requires increased inflammation control [16,17,176]. Created in BioRender.com.