Systematic analysis of different pluripotent stem cell-derived cardiac myocytes as potential testing model for cardiocytoprotection.

INTRODUCTION: Stem cell-derived cardiac myocytes are potential sources for testing cardiocytoprotective molecules against ischemia/reperfusion injury in vitro. MATERIALS AND METHODS: Here we performed a systematic analysis of two different induced pluripotent stem cell lines (iPSC 3.4 and 4.1) and an embryonic stem cell (ESC) line-derived cardiac myocytes at two different developmental stages. Cell viability in simulated ischemia/reperfusion (SI/R)-induced injury and a known cardiocytoprotective NO-donor, S-nitroso-n-acetylpenicillamine (SNAP) was tested. RESULTS: After analysis of full embryoid bodies (EBs) and cardiac marker (VCAM and cardiac troponin I) positive cells of three lines at 6 conditions (32 different conditions altogether), we found significant SI/R injury-induced cell death in both full EBs and VCAM+ cardiac cells at later stage of their differentiation. Moreover, full EBs of the iPS 4.1 cell line after oxidative stress induction by SNAP was protected at day-8 samples. CONCLUSION: We have shown that 4.1 iPS-derived cardiomyocyte line could serve as a testing platform for cardiocytoprotection.

Starch nanocapsules containing a novel neutrophil elastase inhibitor with improved pharmaceutical performance.

Psoriasis and atopic dermatitis patients show an excessive amount of elastase in peripheral blood neutrophils due to an imbalance between this proteolytic enzyme and its endogenous inhibitors, the search for new human neutrophil elastase (HNE) inhibitors are required. The HNE is an attractive therapeutic target and inhibitors with new molecular architectures have been extensively investigated. In this context a promising novel synthetic human neutrophil elastase inhibitor (ER143) was associated to a starch-based nanoparticulate system (StNC) with improved pharmaceutical performance, using a quality by design approach to support product development and optimization. The resulting formulation was characterized in terms of and in vitro release, permeation and retention studies in newborn pig skin, using Franz diffusion cells revealing the StNC have the ability to control the drug release rate and contribute to a high skin retention and/or permeation profiles. The anti-inflammatory activity accessed in vivo using the croton oil-induced ear inflammation model in mice showed that erythema and edema were attenuated in 98% following local application. These observations suggest the association of ER143 to the StNC promotes a deeper skin penetration and retention, also confirming StNC as a potential topical delivery system.