Nebulization of Cyclic Arginine-Glycine-(D)-Aspartic Acid-Peptide Grafted and Drug Encapsulated Liposomes for Inhibition of Acute Lung Injury

• Published in: Pharmaceutical research 2018-05, Vol.35 (5), p.94-15, Article 94
• Main Authors: Desu, Hari R., Thoma, Laura A., Wood, George C.
• Format: Article
• Language: English
• Subjects: Acute Lung Injury - drug therapy; Acute Lung Injury - immunology; Acute Lung Injury - pathology; Acute respiratory distress syndrome; Administration, Inhalation; Alveoli; Amino acids; Animals; Arginine; Aspartic acid; Biochemical markers; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Capillaries - metabolism; Chemokines; Computer simulation; Corticosteroids; Disease Models, Animal; Drug delivery; Drug delivery systems; Drugs; Edema; Effector cells; Encapsulation; Endothelial cells; Endothelium; Formulations; Glycine; Grafting; Humans; IL-1β; Inflammation; Interleukin-1beta - administration & dosage; Interleukin-1beta - immunology; Interleukin-1beta - metabolism; Interleukins; Liposomes; Lungs; Male; Medical Law; Membrane permeability; Methylprednisolone; Methylprednisolone Hemisuccinate - administration & dosage; Nebulizers and Vaporizers; Neutrophils - drug effects; Neutrophils - immunology; Peptides; Peptides, Cyclic - administration & dosage; Permeability; Permeability - drug effects; Pharmacology/Toxicology; Pharmacy; Pulmonary Alveoli - cytology; Pulmonary Alveoli - metabolism; Rats; Rats, Sprague-Dawley; Research Paper; Respiratory tract; Rodents; Sodium; Sodium succinate; Spatial discrimination; Treatment Outcome; Vehicles
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-018-2366-9

Purpose Acute lung injury (ALI) is a fatal syndrome in critically ill patients. It is characterized by lung edema and inflammation. Numerous pro-inflammatory mediators are released into alveoli. Among them, interleukin-1beta (IL-1β) causes an increase in solute permeability across the alveolar-capillary barrier leading to edema. It activates key effector cells (alveolar epithelial and endothelial cells) releasing inflammatory chemokines and cytokines. The purpose of the study was to demonstrate that nebulized liposomes inhibit ALI in vivo . Methods In vivo ALI model was simulated through intra-tracheal instillation of IL-1β solution (100 μg/mL in PBS, pH 7.2, 200 μL) in male Sprague-Dawley rats. Various formulations were tested in ALI induced rats. These formulations include plain liposomes (PL), methylprednisolone sodium succinate solution (MPS solution), cRGD-peptide grafted liposomes (L cRGD ) and methylprednisolone sodium succinate encapsulated and cRGD-peptide grafted liposomes (MPS-L cRGD ). Formulations were nebulized in vivo in rats using micro-pump nebulizer. Results Liposome formulations exhibited higher levels of drug concentration in lungs. The physicochemical parameters demonstrated that the liposome formulations were stable. On the basis of aerodynamic droplet-size, nebulized formulations were estimated to deposit in different regions of respiratory tract, especially alveolar region, Among the formulations, MPS-L cRGD caused significant reduction of edema, neutrophil infiltration and inflammation biochemical marker levels. Conclusion From the results, it can be inferred that nebulization of targeted liposomes had facilitated spatial and temporal modulation of drug delivery resulting in alleviation of ALI.