Lipid Nanoparticles as Delivery Vehicles for Inhaled Therapeutics

Abstract

Lipid nanoparticles (LNPs) have emerged as a powerful non-viral carrier for drug delivery. With the prevalence of respiratory diseases, particularly highlighted by the current COVID-19 pandemic, investigations into applying LNPs to deliver inhaled therapeutics directly to the lungs are underway. The progress in LNP development as well as the recent pre-clinical studies in three main classes of inhaled encapsulated drugs: small molecules, nucleic acids and proteins/peptides will be discussed. The advantages of the pulmonary drug delivery system such as reducing systemic toxicity and enabling higher local drug concentration in the lungs are evaluated together with the challenges and design considerations for improved formulations. This review provides a perspective on the future prospects of LNP-mediated delivery of inhaled therapeutics for respiratory diseases.

Keywords: inhalation drug delivery; lipid nanoparticles (LNPs); lung; respiratory diseases.

Figure 1

Visual illustration of the structures and composition of various LNPs. (A) Liposome. (B) Drug-loaded liposome. (C) Targeted liposome. (D) PEGylated liposome. (E) Solid lipid nanoparticle. (F) Nanostructured lipid carrier. Created with BioRender.com.

Figure 2

A summary of inhaled LNP-encapsulated drugs that have been investigated for respiratory diseases in animal models. Created with BioRender.com. ALI: Acute lung injury; ARDS: acute respiratory distress syndrome; COPD: chronic obstructive pulmonary disease; CF: Cystic fibrosis; IPF: idiopathic pulmonary fibrosis; LAM: lymphangioleiomyomatosis; LNP: lipid nanoparticle; NSCLC: non-small cell lung carcinoma; PAH: pulmonary arterial hypertension; PCD: primary ciliary dyskinesia; SLN: solid lipid nanoparticles; NLC: nanostructured lipid carriers; VIP: vasoactive intestinal peptide.

Figure 3

Schematic summary of AD-dependent deposition and distribution mechanisms of inhaled LNP aggregates in the airways. The mechanisms are inertial impaction, gravitation sedimentation and Brownian diffusion. Subsequent cellular uptake of individual LNPs and drug payloads by dissociation, endocytosis and membrane fusion facilitate therapeutic action (PEGylated and targeted liposome depicted). AD: aerodynamic diameter. Created with BioRender.com.