Biomimetic Cardiac Fibrotic Model for Antifibrotic Drug Screening.

Cardiac fibrosis is characterized by pathological proliferation and activation of cardiac fibroblasts to myofibroblasts. Inhibition and reverse of transdifferentiation of cardiac fibroblasts to myofibroblasts is a potential strategy for cardiac fibrosis. Despite substantial progress, more effort is needed to discover effective drugs to improve and reverse cardiac fibrosis. The main reason for the slow development of antifibrotic drugs is that the traditional polystyrene culture platform does not recapitulate the microenvironment where cells reside in tissues. In this study, we propose an in vitro cardiac fibrotic model by seeding electrospun yarn scaffolds with cardiac fibroblasts. Our results show that yarn scaffolds allow three-dimensional growth of cardiac fibroblasts, promote extracellular matrix (ECM) deposition, and induce the transdifferentiation of cardiac fibroblasts to myofibroblasts. Exogenous transforming growth factor-ß1 further promotes cardiac fibroblast activation and ECM deposition, which makes it a suitable fibrotic model to predict the antifibrotic potential of drugs. By using this platform, we demonstrate that both Honokiol (HKL) and Pirfenidone (PFD) show potential in antifibrosis to some extent. HKL is more efficient in antifibrosis than PFD as revealed by biochemical composition, gene, and molecular analyses as well as histological and biomechanical analysis. The electrospun yarn scaffold provides a novel platform for constructing in vitro fibrotic models to study cardiac fibrosis and to predict the antifibrotic efficacy of novel drugs.

Polyethylenimine and sodium cholate-modified ethosomes complex as multidrug carriers for the treatment of melanoma through transdermal delivery.

Aim: Multidrug resistance is the main reason for the failure of chemotherapy during the treatment of the tumor. To overcome multidrug resistance, this study attempts to develop a novel transdermal drug-delivery system (TDDS) loading cytotoxic drug and chemosensitizer. Materials & methods: The polyethylenimine-modified ethosomes (Eth-PEI) and sodium cholate-modified ethosomes (Eth-SC) were firstly fabricated, and then a novel TDDS based on the carriers complex of Eth-PEI/Eth-SC was prepared by electrostatic interaction and evaluated both in vitro and in vivo. Results: The Eth-PEI/Eth-SC showed the excellent antitumor effect on treating melanoma, using doxorubicin and curcumin as the cytotoxic drug and chemosensitizer, respectively. Conclusion: The as-prepared TDDS composed of Eth-PEI/Eth-SC loading multidrug is an effective means for treating melanoma.