Preparation and evaluation of inhalable S-allylmercapto-N-acetylcysteine and nintedanib co-loaded liposomes for...

Area of Science:

• Nanomedicine
• Pharmacology
• Pulmonary Medicine

Background:

• Oral nintedanib (NDNB) and pirfenidone for pulmonary fibrosis (PF) have high doses and severe side effects.
• NDNB elevates galectin-3, activating NF-κB and causing inflammation.
• S-allylmercapto-N-acetylcysteine (ASSNAC) inhibits TLR-4/NF-κB, alleviating inflammation.

Purpose of the Study:

• To design and prepare inhalable ASSNAC and NDNB co-loaded liposomes for pulmonary fibrosis treatment.
• To evaluate the efficacy and safety of inhaled liposomal drug delivery for PF.
• To investigate the synergistic effects of ASSNAC and NDNB in treating pulmonary fibrosis.

Main Methods:

• Co-loaded liposomes of ASSNAC and NDNB were prepared and characterized (size, zeta potential).
• Inhalable properties (FPF, MMAD) were assessed for nebulized liposome solutions.
• In vivo and in vitro studies evaluated drug deposition, retention, mucus permeability, and anti-fibrotic effects.

Main Results:

• Inhalable liposomes (98.32±1.98 nm) with good aerodynamic properties were produced.
• Inhalation enhanced lung drug deposition and retention, with DSPE-PEG 2000 improving mucus permeability.
• ASSNAC mitigated NDNB-induced TLR-4/NF-κB activation, reducing side effects.
• Inhaled NDNB/liposomes showed superior or comparable anti-fibrotic effects to oral NDNB at a 30x lower dose.
• The ASSNAC and NDNB combination demonstrated greater efficacy than single drugs for pulmonary fibrosis.

Conclusions:

• Inhalable ASSNAC/NDNB co-loaded liposomes represent a promising, safer, and more effective treatment strategy for pulmonary fibrosis.
• This novel drug delivery system overcomes limitations of oral administration, improving therapeutic outcomes.
• The combination therapy offers a synergistic approach to combatting pulmonary fibrosis.