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Investigation of cell death mechanism and activity of esculetin-loaded PLGA nanoparticles on insulinoma cells in vitro.

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Date
2020-01-24T00:00:00Z
Authors
Bahadori, F
Karatug, Kacar
Kepekci, Tekkeli
Topcu, GÜLAÇTI
Bolkent, S
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Abstract
Aim The purpose of this study was to prepare targeted cancer therapy formulation against insulinoma INS-1 cells and to study its effect on cell death with related mechanisms in vitro. Methods Polylactide-co-glycolide (PLGA) nano-micelles were used for preparation of esculetin nano-formulation (nano-esculetin). The cells were treated with nano-esculetin and free esculetin. Apoptotic and necrotic cell death percentages, cell proliferation, ATP and GTP reductions and insulin levels were investigated on insulinoma INS-1 cells for both free and nano-esculetin formulations. Results About 50 mg of PLGA was able to carry 20 mg esculetin in 20 ml of formulation. The obtained optimized formulation was 150 nm, with 92% encapsulation efficiency and a slow-release behaviour was observed during release studies. Nano-esculetin bearing 25, 50 and 100 mu g esculetin and free esculetin in equivalent doses successfully decreased cell viability. The prevailing cell death mechanism was necrosis. Along with cell proliferation, intracellular insulin and the ratio of ATP and GTP were decreased even with 12.5, 25 and 50 mu g esculetin bearing nano-formulation and its equivalent free esculetin. Conclusions The results revealed that esculetin is able to show its anti-tumor afficacy after loading to PLGA nano-micelles and nano-encapsulation intensifies its cytotoxic activity in vitro. Current study shows that esculetin and its nano formulations are promising agents in treatment of insulinoma.
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Karatug K., Bahadori F., Kepekci T., Topcu G., Bolkent S., -Investigation of cell death mechanism and activity of esculetin-loaded PLGA nanoparticles on insulinoma cells in vitro.-, The Journal of pharmacy and pharmacology, 2020
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