Strategies to Overcome Biological Barriers Associated with Pulmonary Drug Delivery

Abstract

While the inhalation route has been used for millennia for pharmacologic effect, the biological barriers to treating lung disease created real challenges for the pharmaceutical industry until sophisticated device and formulation technologies emerged over the past fifty years. There are now several inhaled device technologies that enable delivery of therapeutics at high efficiency to the lung and avoid excessive deposition in the oropharyngeal region. Chemistry and formulation technologies have also emerged to prolong retention of drug at the active site by overcoming degradation and clearance mechanisms, or by reducing the rate of systemic absorption. These technologies have also been utilized to improve tolerability or to facilitate uptake within cells when there are intracellular targets. This paper describes the biological barriers and provides recent examples utilizing formulation technologies or drug chemistry modifications to overcome those barriers.

Evaluation and Selection of the Inhaler Device for Treprostinil Palmitil Inhalation Powder

“…To overcome the pulmonary barriers for inhaled drugs with poor pharmacokinetics and extend the duration of pharmacological effect, formulation strategies (Cipolla and Gonda, 2011) as well as prodrug strategies (Chen et al, 2021;Plaunt et al, 2022) have been explored. Both strategies have been applied to TRE including the recent development of a prodrug of TRE, treprostinil palmitil (TP), initially formulated as a lipid nanoparticle to provide prolonged exposure of TP in the lung fluid after inhalation (Leifer et al, 2018).…”

Liposomes or Extracellular Vesicles: A Comprehensive Comparison of Both Lipid Bilayer Vesicles for Pulmonary Drug Delivery

“…Many drug delivery systems (e.g., NPs, MPs, solid lipid NPs, nanostructured lipid carriers, polymer-drug conjugates, macromolecules (dendrimers), lipid vesicles (LPs, pro-LPs), and recently EVs) fulfill a variety of biopharmaceutical requirements, including adequate drug loading, protecting the actives from deterioration, and ensuring biocompatibility, biodegradability, and stability during aerosolization. However, a significant drawback of these systems is their ease of exhalation from the lungs following inhalation [ 257 ]. Although LPs for pulmonary delivery have been prevalent for many decades, they are expected to be bypassed by EVs and hybrid vesicles when appropriate formulation techniques are improved.…”

Novel Approaches for Overcoming Biological Barriers

“…[13]. The comprehensive review by Plaunt et al [14] highlighted the recent examples of how the barriers of pulmonary delivery can be overcome using formulation technologies or modifying the chemistry of the compound (drug).…”