Am80-Encapsulated Lipid Nanoparticles, Developed with the Aim of Achieving Alveolar Regeneration, Have an Improvement Effect on Pulmonary Emphysema

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis and emphysema, and current drug treatments target its symptoms. Thus, the development of a therapeutic drug to repair alveolar destruction is urgently needed. Our previous research revealed that the synthetic retinoic acid Am80 (1.0 mg/kg) showed a repairing effect on collapsed alveoli in a mouse model of elastase-induced emphysema. However, a further reduction in the dose is desirable to facilitate the development of a powder inhalation formulation for clinical application. We, therefore, focused on SS-OP to deliver Am80 efficiently. As a result, 0.01 mg/kg of Am80-encapsulated SS-OP nanoparticles repaired collapsed alveoli and improved the respiratory function in the mouse model of elastase induced emphysema. The results suggested that, with the use of SS-OP, the Am80 dose could be reduced. This could contribute to the development of a powder inhalation system as a curative medicine for COPD.

Intracellular Drug Delivery Process of Am80-Encapsulated Lipid Nanoparticles Aiming for Alveolar Regeneration

“…Furthermore, the surface is destabilized by the cleavage of the intramolecular disulfide bond by glutathione in the cytoplasm; the drug is released via self-disintegration through the intraparticle reaction between the resulting thiol group and the intramolecular phenyl ester, such that efficient drug delivery to the cytoplasm can be expected [ 22 ]. Recently, we reported that Am80-encapsulated SS-OP nanoparticles showed a therapeutic effect in a mouse model of COPD at a dose that was 1/100 that of Am80 [ 23 ]. In this previous report, we were able to show pharmacological effects at different doses in the free Am80 and Am80-encapsulated SS-OP nanoparticles, but it was unclear whether there were differences in the nuclear translocation of Am80.…”