Akademik Veri Yönetim Sistemi
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, sa.7, ss.671-686, 2024 (SCI-Expanded)
Objective: This study was aimed to develop a cationic lipoplex formulation loaded with Nintedanib and miR-29b (LP-NIN-miR) as an alternative approach in the combination therapy of idiopathic pulmonary dibrosis (IPF) by proving its additive anti-fibrotic therapeutic effects through in vitro lung fibrosis model. Significance: This is the first research article reported that the LP-NIN-MIR formulations in the treatment of IPF. Methods: To optimize cationic liposomes (LPs), quality by design (QbD) approach was carried out. Optimized blank LP formulation was prepared with DOTAP, CHOL, DOPE, and DSPE-mPEG 2000 at the molar ratio of 10:10:1:1. Nintedanib loaded LP (LPs-NIN) were produced by microfluidization method and were incubated with miR-29b at room temperature for 30 min to obtain LP-NIN-miR. To evaluate the cellular uptake of LP-NIN-miR, NIH/3T3 cells were treated with 20 ng.mL(-1) transforming growth factor-beta 1 (TGF-beta 1) for 96 h to establish the in vitro IPF model and incubated with LP-NIN-miR for 48 h. Results: The hydrodynamic diameter, polydispersity index (PDI), and zeta potential of the LP-NIN-miR were 87.3 +/- 0.9 nm, 0.184 +/- 0.003, and +24 +/- 1 mV, respectively. The encapsulation efficiencies of Nintedanib and miR-29b were 99.8% +/- 0.08% and 99.7% +/- 1.2%, respectively. The results of the cytotoxicity study conducted with NIH/3T3 cells indicated that LP-NIN-miR is a safe delivery system. Conclusions: The outcome of the transfection study proved the additive anti-fibrotic therapeutic effect of LP-NIN-miR and suggested that lipoplexes are effective delivery systems for drug and nucleic acid to the NIH/3T3 cells in the treatment of IPF.