Yanmin Pei, Meidong Si, Xuemei Ma, Siyun Liu, Fang Zhao, Ru Zhou
Ningxia Medical University and General Hospital of Ningxia Medical University.
China
Drug Design, Development and Therapy
Drug Des Dev Ther 2025; 19: 11119-11144
DOI: 10.2147/DDDT.S547530
Abstract
Purpose: 18β-Glycyrrhetinic acid liposomes (18β-GA-Lips) were developed to enhance lung-specific drug delivery and optimize the therapeutic management of pulmonary arterial hypertension (PAH).
Methods: 18β-GA-Lips of varying particle sizes were formulated using the film-dispersion method and the thin-film dispersion-probe ultrasonic technique. Their characteristics, pharmacokinetics, and tissue distribution were thoroughly investigated, followed by an inhalation subacute toxicological analysis. Anti-PAH effects were assessed through hemodynamic measurements, right ventricular hypertrophy evaluation, echocardiography, histomorphometric, and morphological analyses.
Results: The 18β-GA-Lips, with varying particle sizes, exhibited a uniform spherical morphology, achieved entrapment efficiencies exceeding 80%, and had average particle sizes ranging from 150 to 1183 nanometers. These were categorized into four distinct size groups. The drug release profile demonstrated favorable sustained-release characteristics in vitro, and the formulation remained stable for up to 15 days when stored at 4°C. Pharmacokinetic analyses revealed that, compared with the 18β-GA-solution group, the AUC(0→48), MRT(0→48), t1/2, tmax, and clearance rate of 18β-GA-Lips in each group were 4.42, 3.27, 4.28, 5.07, 2.10, 3.41, 1.73, 1.46, 1.53, 1.32, 1.79, 1.67, 0.61, 2.11, 0.71, 1.71, 1.15, 0.62, 0.96, and 0.90 times higher, respectively. Tissue distribution studies revealed that B-18β-GA-Lips exhibited the highest lung-targeting efficiency, with a Te value of 54.13%. No apparent signs of toxicity were observed. In vivo data demonstrate that rats treated with 18β-GA in different formulations (solution and liposomal) and with NO exhibited significantly lower mPAP and RVSP compared to the SuHx group, with no statistically significant differences observed among the treatment groups. Notably, 18β-GA-Lips exhibited a more pronounced reduction in RVHI compared to oral solutions and significantly attenuated pulmonary vascular remodeling. Furthermore, pharmacodynamic evaluations indicated that 18β-GA-Lips exhibited superior inhibitory effects on PAH in rats compared to both atomized and intragastric 18β-GA solutions.
Conclusion: These findings confirm that 18β-GA-Lips exhibit outstanding lung-targeting capabilities and lack inhalation toxicity, thereby significantly enhancing the therapeutic efficacy of treatments for PAH.
Category
Medical Therapy. Pharmacokinetics and Pharmacology
Medical Therapy. Efficacy or Lack of Efficacy
Medical Therapy. Adverse Effects or Lack of Adverse Effects
Animal Models of Pulmonary Vascular Disease and Therapy
Class I. Drug-induced and Toxin-induced Pulmonary Hypertension
Class III. Pulmonary Hypertension Associated with Alveolar Hypoxia
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes