IP: 79.110.28.119 On: Tue, 19 Feb 2019 10:10:10 Copyright: American Scientific Publishers Delivered by Ingenta Copyright © 2019 American Scientific Publishers All rights reserved Printed in the United States of America Article Journal of Nanoscience and Nanotechnology Vol. 19, 3706–3719, 2019 www.aspbs.com/jnn Novel Approach to the Treatment of Diabetes: Embryonic Stem Cell and Insulin-Loaded Liposomes and Nanocochleates Çi˘ gdem Yücel 1 , Ye¸ sim Akta¸ s 1 , Zelihagül De˘ gim 2 ∗ ,¸ Sükran Yılmaz 3 , Taibe Arsoy 3 , Levent Altınta¸ s 4 , Can Çokçalı¸ skan 3 , and Mahmut Sözmen 5 1 Department of Pharmaceutical Technology, Erciyes University Faculty of Pharmacy, 38039 Kayseri, Turkey 2 Department of Pharmaceutical Technology, Biruni University Faculty of Pharmacy, 34010 Topkapı ˙ Istanbul, Turkey 3 Food and Mouth Diseases Institute, 06520, Ankara, Turkey 4 Department of Pharmacology and Toxicology, Ankara University Faculty of Veterinary Medicine, 06110 Ankara, Turkey 5 Department of Pathology, 19 Mayıs University Faculty of Veterinary Medicine, 55220 Samsun, Turkey This study aims to investigate and compare the effects of insulin and embryonic stem-cell (ESC) loaded liposomes (LPs) and nanocochleate formulations and their PEGylated forms on the glucose levels. All formulations were characterized considering particle size, zeta potential, polydispersity index and encapsulation efficiencies. In-vitro insulin that releases from the formulations was deter- mined using Franz-type diffusion cells. A cytotoxicity test revealed that none of the formulations was toxic to cells in any concentrations. The effects of the formulations on diabetic cells induced with glucose and streptozotocin (STZ) were then investigated in cell culture studies. Although glucose levels were decreased by the formulations after incubation, the liposomal formulations were found to be better. In experiments that were conducted on mice, it was observed again that blood glu- cose levels decreased successfully when diabetic pancreatic beta TC cells were incubated with the formulations, and all formulations were found to be effective in decreasing blood glucose levels in diabetic mice. Although ESC-loaded LPs were found to be the most effective formulation, LPs and nanocochleate formulations may also be used for the repair of pancreatic cells. This proposed ESC treatment is considered to be an attractive approach and a potential source for cell replacement therapy in the treatment of diabetes. Keywords: Embryonic Stem Cell, Insulin, Liposome, Nanocochleate, Diabetes, Pancreatic Beta TC Cell. 1. INTRODUCTION Diabetes is a complex metabolic disorder that may lead to severe complications, such as kidney failure, heart disease, stroke, blindness and early death. 1 2 There are two general forms of diabetes: Type 1 diabetes, also known as juvenile-onset diabetes, and Type 2 diabetes, referring to adult-onset diabetes. 1 3 Type 2 diabetes is characterized by peripheral insulin resistance with an insulin-secretory defect and beta (-cell dysfunction. 4 5 Defects in  cells in the Langerhans islets bring about insulin insufficiency or deficiency, 6 and insulin therapy is the oldest and most effective glucose-lowering treat- ment available, which works by improving the control ∗ Author to whom correspondence should be addressed. of blood glucose levels and prevents diabetic patients from long-term complications. 5 Insulin is administrated via a subcutaneous route with an injection, which has the disadvantages of pain, infection possibility or trauma at the injection site, resulting in low patient compliance. 7 In recent years, diabetic stem-cell studies have seen a rise in popularity owing to the possibility of obtaining  cells from different sources or the replication of mature cells. Embryonic stem cells (ESC) are derived from the inner cell mass of 3–5-day old embryos, 8 9 and have the potential to become any type of specialized cells, including insulin-secreting functional  cells. 3 Liposomes can encapsulate both hydrophilic and hydrophobic drugs in the aqueous core and/or the phos- pholipid membrane and are effective vehicles for drug 3706 J. Nanosci. Nanotechnol. 2019, Vol. 19, No. 7 1533-4880/2019/19/3706/014 doi:10.1166/jnn.2019.16321