Introduction: Colloidal polymeric pirfenidone nanoparticles (Pirf-Nps) have huge potential for targeted drug delivery in IPF treatment. Their efficacy on epithelial mesenchymal transition (EMT) by modulating TGF-β induced intracellular signaling via SMAD-2/3 transcription factors and downstream regulation of profibrotic gene expression such as collagens, matrix metalloproteases remains to be elaborated. Methodology: MePEG-PCL diblock nanoparticles were synthesized by ring opening polymerization and double emulsion solvent technique. Nps were characterized by Nanosight, DLS, TEM, FTIR and drug loading and release efficiency was examined. The efficacy of Pirf-Nps was studied on A549 cell lines: Group-I- Saline, Group-II- bleomycin (50mM), Group III- Bleomycin +Pirfenidone (520µg/ml) and Group IV- Bleomycin+ Pirf- PCL-PEG Nps at different time intervals- 4,6,8,24,48 hours. Cells were harvested and TGFβ1, SMAD-2,3 mRNA levels were evaluated. Result: Bleomycin instillation resulted in bimodal increase in TGFβ1, SMAD-2,3 gene expression initially at 2 hours and then at 24/48 hours and correlated with EMT of alveolar epithelial cells. Pirfenidone, standard dose decreased gene expression of TGF β1 and SMAD-2,3 at 48 hrs. Pirf-Nps were used at 4.7 x 107Nps/ml concentration. The surface morphology of Pirf-PCL-PEG Nps was spherical with mean size 181 nm. The loading and releasing efficiency of Nps was calculated and Pirf-PCL-PEG NPs were administered at serial dilution. Pirf-PCL-PEG NPs efficiently reversed the EMT caused by bleomycin. Discussion and Conclusion: We demonstrate the in vitro efficacy of nanoscopic drug delivery system in targeting the gene expression and reducing the TGF β1 and SMAD2/3 induced EMT caused by bleomycin.

Pirfenidone NPs modulate TGFβ1- SMAD expression and attenuate EMT in lung cancer cell line

2019 Fall National Meeting

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