Combinatorial treatment of idiopathic pulmonary fibrosis using nanoparticles with prostaglandin E and siRNA(s)

Abstract

Inhalation delivery of prostaglandin E (PGE2) in combination with selected siRNA(s) was proposed for the efficient treatment of idiopathic pulmonary fibrosis (IPF). Nanostructured lipid carriers (NLC) were used as a delivery system for PGE2 with and without siRNAs targeted to MMP3, CCL12, and HIF1Alpha mRNAs. The model of IPF was developed in SKH1 mice by intratracheal administration of bleomycin at a dose of 1.5U/kg. Results showed that NLC-PGE2 in combination with three siRNAs delivered locally to the lungs by inhalation markedly reduced mouse body mass, substantially limited hydroxyproline content in the lungs and disturbances of the mRNAs and protein expression, restricted lung tissue damage and prevented animal mortality. Our data provide evidence that IPF can be effectively treated by inhalation of the NLC-PGE2 in combination with siRNAs delivered locally into the lungs. This effect could not be achieved by using NLC containing just PGE2 or siRNA(s) alone.