In silico screening and validation of natural compounds with fabrication and characterization of a lead compound-loaded chitosome for targeting lung fibrosis†

Abstract

Lung fibrosis (LF) is a serious complication with very limited therapeutic options. This study aimed to find a potential compound for targeting LF and develop a chitosome formulation to minimize any inherent drawbacks of the compound and achieve effective drug delivery. In total, 79 natural compounds were screened using an in silico approach against five targeted proteins (3HMG, 6B8Y, 2FAP, 3CQU, and 3DK9). Amongst these, quercetin (QER) exhibited the best efficacy (−14.725 kcal mol⁻¹) and ΔG average (−86.45 ± 6.24) kcal mol⁻¹ against the TGF-β receptor (PDB ID: 6B8Y). In vitro studies revealed that bleomycin-challenged A549 cells showed a fibrosis-like behaviour. Upon treatment with QER, the cell viability decreased owing to a reduction in the mitochondrial membrane potential and increased apoptosis. Furthermore, cell migration was inhibited with an improvement in cellular morphology. A QER-loaded chitosome formulation (QCF) was prepared through modified thin-film hydration. Variables were optimized using a response surface methodology Box–Behnken design. The QCF was further characterized on the basis of microscopic observation, zeta potential, entrapment efficiency, drug release and kinetics and by evaluating the effect of temperature on the QCF. Its zeta potential was +24.83 ± 0.32 mV, while microscopic observation showed that it had a spherical morphology with slightly rough surfaces after chitosan coating. Furthermore, the EE% was determined to be 81.75 ± 0.46%. The QCF also demonstrated a 74.23 ± 1.01% release of QER till 24 h, following Higuchi model kinetics. In conclusion, the in silico and in vitro cell line studies provided evidence for QER as a lead molecule for targeting LF. Moreover, the prepared QCF demonstrated sustained release with prospective QER targeted delivery. However, further extensive research is required to provide a promising strategy for the management of LF in the future.