Efficient Delivery to Human Lung Fibroblasts (WI-38) of Pirfenidone Incorporated into Liposomes Modified with Truncated Basic Fibroblast Growth Factor and Its Inhibitory Effect on Collagen Synthesis in Idiopathic Pulmonary Fibrosis

Abstract

In the present in vitro study, we assessed the delivery of pirfenidone incorporated into liposomes modified with truncated basic fibroblast growth factor (tbFGF) to lung fibroblasts and investigated the antifibrotic effect of the drug. The tbFGF peptide, KRTGQYKLC, was used to modify the surface of liposomes (tbFGF-liposomes). We used the thin-layer evaporation method, followed by sonication, to prepare tbFGFliposomes containing pirfenidone. The cellular accumulation of tbFGF-liposomes was 1.7-fold greater than that of non-modified liposomes in WI-38 cells used as a model of lung fibroblasts. Confocal laser scanning microscopy showed that tbFGF-liposomes were widely localized in WI-38 cells. The inhibitory effects of pirfenidone incorporated into tbFGF-liposomes on transforming growth factor-β1 (TGF-β1)-induced collagen synthesis in WI-38 cells were evaluated by measuring the level of intracellular hydroxyproline, a major component of the protein collagen. Pirfenidone incorporated into tbFGF-liposomes at concentrations of 10, 30, and 100 µM significantly decreased the TGF-β1-induced hydroxyproline content in WI-38 cells. The antifibrotic effect of pirfenidone incorporated into tbFGF-liposomes was enhanced compared with that of pirfenidone solution. These results indicate that tbFGF-liposomes are a useful drug delivery system of anti-fibrotic drugs to lung fibroblasts for the treatment of idiopathic pulmonary fibrosis.

Liposomal hydrogel formulation for transdermal delivery of pirfenidone

“…The EE was not significantly (p40.05) different among the different pH conditions (4, 7 and 10) studied (Supplementary Figure S2). This is attributed to the neutral charge of PFD (Togami et al, 2015).…”

“…Because of the inherent permeability limitations of skin barrier, we have encapsulated PFD in a well-characterized liposomal delivery system. However, PFD with aqueous solubility of 15 mg/mL (Togami et al, 2015) poses a challenge in encapsulation into liposomal vesicles. The encapsulation of PFD in liposomes through conventional preparation method of TFH resulted in poor EE.…”

Spermidine-mediated poly(lactic-<em>co</em>-glycolic acid)&nbsp;nanoparticles containing fluorofenidone for the treatment of idiopathic pulmonary fibrosis

“…27 Encapsulating antifibrotic drugs within biodegradable polymers to form microspherical particles has been reported in a lung-targeting drug-delivery system. 28 Great attention has been paid to the use of polymeric nanoparticles (NPs) as delivery vehicles for lung-disease drugs, and some studies have suggested that nanocarriers can significantly enhance antifibrotic drug efficacy. [29][30][31][32] Local delivery of biodegradable PD NPs has exhibited high dispersibility and suitable distribution for inhalation therapy, with sustained lung delivery and enhanced antifibrotic efficacy.…”

“…[41][42][43][44] Based on this evidence, PLGA-NPs releasing AKF are proposed as a potential therapeutic measure for IPF. Furthermore, through the conjugation of a targeting agent, such as truncated bFGF peptide 28 or aptamer 45 to an NP surface, an active-targeting effect could be established to modify the pharmacokinetics of drugs and further enhance therapeutic efficiency.…”

Tissue-Clearing Techniques Enable Three-Dimensional Visualization of Aerosolized Model Compound and Lung Structure at the Alveolar Scale

“…These findings suggest that tissue-clearing treatment is useful for the study of intrapulmonary distribution and the development of pulmonary drug delivery systems targeting both the lung surface (e.g., epithelial lining fluid) 21) and lung cells such as alveolar epithelial cells, 22) alveolar macrophages, 7) and lung fibroblasts. 23) For the accurate and detailed evaluation of drug distribution in the lungs, future studies must develop a means of visually identifying these lung cell types.…”