New inhalable therapy strongly combats IPF lung scarring in mice
Nanoparticle treatment was better tolerated than approved medicine: Study
A novel inhalable therapy has shown promise for treating idiopathic pulmonary fibrosis (IPF) by outperforming an approved oral medicine in a mouse study.
The new treatment, called VB-RT NPs, consists of lipid nanoparticles loaded with two medicines, verteporfin and berbamine, designed to disrupt both the mechanical stiffness and biochemical signals that drive IPF. The inhaled formulation significantly reduced signs of fibrosis in mice and was better tolerated than the oral approved IPF therapy pirfenidone (sold as Esbriet).
“The results demonstrate that VB-RT NPs effectively … halted fibrosis progression, offering a promising therapeutic approach for IPF,” researchers wrote.
The study, “Pulmonary-Targeted Nanoparticles Interrupt the Malignant Mechanical and Biochemical Signaling Crosstalk for Idiopathic Pulmonary Fibrosis Therapy,” was published in Advanced Science.
Understanding IPF and its drivers
IPF is a progressive lung disorder characterized by excessive accumulation of scar tissue in the lungs, leading to symptoms such as shortness of breath, especially with exertion, fatigue, and a dry, hacking cough.
Scar formation is driven by biochemical signals that overactivate cells called myofibroblasts, which increase lung tissue stiffness by depositing collagen, the main protein in scar tissue. Together, these biochemical signals and the resulting mechanical stiffening contribute to the progression of IPF.
Researchers in China developed the inhalable formulation to disrupt both biochemical and mechanical signals that drive IPF. Berbamine restrains fibrosis triggered by biochemical signaling, while verteporfin suppresses the conversion of mechanical forces to biochemical stimuli.
“Targeting the malignant … mechanical and biochemical signaling crosstalk represents a promising therapeutic strategy for IPF,” the researchers wrote.
The VB-RT NPs involve loading the two medicines in lipid nanoparticles coated in tannic acid and L-arginine to enhance retention and penetration deep into lung tissue.
VB-RT NP treatment significantly reduced lung tissue abnormalities by decreasing collagen deposition, thickening of the alveolar walls (the walls of the lung’s air sacs), and fluid accumulation. The extent of lung fibrosis was also reduced, in contrast to treatment with oral pirfenidone, which showed no noticeable improvements in these areas.
On a molecular level, the lungs of untreated IPF mice had more than twice the levels of hydroxyproline, a major component of collagen, compared with healthy mice. VB-RT NP treatment reduced hydroxyproline by 2.42 times, whereas pirfenidone reduced it by 1.7 times.
VB-RT NP treatment reduced the average lung stiffness in IPF mice from 10.56 to 3.45 kPa, approaching the level of healthy lungs (3.25 kPa). Pirfenidone-treated mice remained elevated at 8.39 kPa.
Lung function tests showed significant improvement with VB-RT NPs, approaching values observed in healthy mice. Additionally, body weight progressively declined in untreated IPF mice, while VB-RT NP-treated mice regained body weight to normal levels.
In safety assessments, the lipid nanoparticles had no effect in various organs, including the heart, liver, spleen, kidneys, and eyes. Markers for liver damage were similar to those of healthy controls. By contrast, mice receiving oral pirfenidone exhibited significantly elevated levels of liver damage markers.
“Our study highlights a promising therapeutic strategy to interrupt the malignant crosstalk between mechanical and biochemical signaling in IPF lungs,” the researchers concluded. “This strategy may also be applicable to other diseases involving similar signaling crosstalk.”
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