Toxicological assessment of orally delivered nanoparticulate insulin (original) (raw)
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In vivo evaluation of safety and efficacy of self-assembled nanoparticles for oral insulin delivery
2009
A variety of approaches have been studied in the past to overcome the problems encountered with the oral delivery of insulin, but with little success. In this study, self-assembled nanoparticles (NPs) with a pH-sensitive characteristic were prepared by mixing the anionic poly-g-glutamic acid solution with the cationic chitosan solution in the presence of MgSO 4 and sodium tripolyphosphate. The in vitro results found that the transport of insulin across Caco-2 cell monolayers by NPs appeared to be pH-dependent; with increasing pH, the amount of insulin transported decreased significantly. An in vivo toxicity study was performed to establish the safety of the prepared NPs after oral administration. Additionally, the impact of orally administered NPs on the pharmacodynamics (PD) and pharmacokinetics (PK) of insulin was evaluated in a diabetic rat model. The in vivo results indicated that the prepared NPs could effectively adhere on the mucosal surface and their constituted components were able to infiltrate into the mucosal cell membrane. The toxicity study indicated that the NPs were well tolerated even at a dose 18 times higher than that used in the PD/PK study. Oral administration of insulin-loaded NPs demonstrated a significant hypoglycemic action for at least 10 h in diabetic rats and the corresponding relative bioavailability of insulin was found to be 15.1 AE 0.9%. These findings suggest that the NPs prepared in the study are a promising vehicle for oral delivery of insulin.
European Journal of Pharmaceutical Sciences, 2007
Insulin bioactivity a b s t r a c t Insulin-loaded alginate-dextran nanospheres were prepared by nanoemulsion dispersion followed by triggered in situ gelation. Nanospheres were characterized for mean size and distribution by laser diffraction spectroscopy and for shape by transmission electron microscopy. Insulin encapsulation efficiency and in vitro release were determined by Bradford protein assay and bioactivity determined in vitro using a newly developed Western blot immunoassay and in vivo using Wistar diabetic rats. Nanospheres ranged from 267 nm to 2.76 m in diameter and demonstrated a unimodal size distribution. Insulin encapsulation efficiency was 82.5%. Alginate-dextran particles suppressed insulin release in acidic media and promoted a sustained release at near neutral conditions. Nanoencapsulated insulin was bioactive, demonstrated through both in vivo and in vitro bioassays
Nanotechnology and Development of Oral Insulin
Biomedical Journal of Scientific & Technical Research, 2019
Wide researches have been done to investigate the oral delivery system of insulin for the diabetes' treatment. Developments in nanotechnology have brought us ever closer to this purpose. The current review focuses on the various barriers existing in the way of oral insulin delivery and the strategies taken so far to dominate those by restrain nanoparticles as potential carriers of insulin.
Veterinary Sciences: Research and Reviews, 2021
Administration of peptide drugs like insulin through the oral avenue specially the gastro-intestinal tract represents the great challenges. Polymeric nanoparticles are suitable colloidal carriers for insulin delivery. The current study was carried out to evaluate nanoparticle tactics for the oral delivery of insulin in the alloxan-induced hyperglycemia in rat model. Twenty male rats of age four months were randomly allocated into four different groups (T 0 , T 1 , T 2 , and T 3). After acclimatization diabetes was induced in three groups of rats (T 1 ; positive control, T 2 : insulin only insulin, and T 3 ; insulin with nano particles) by administered alloxan injection at dose of 120mg/kg body weight intraperitoneally. Group T 0 was kept for negative control while T 1 was kept positive control. T 2 were considered as insulin treated group at 21IU/kg and T 3 as insulin with nano particles of same dose as insulin. Over the sequence of the experimental trials, observations were noted for blood glucose level, glycosylated hemoglobin, and body weight. Blood glucose levels were increased significantly (P<0.05) in all treated groups compared to the negative control group. Similarly, bodyweight was decreased significantly (P<0.05) in all alloxan treated groups compared to negative control. There was significant falling in blood glucose level in insulin with nanoparticle treated group (T 3) compared to only insulin treated group (T 2) and (T 1) that was received alloxan. The present study shows that insulin administration of oral route with nanoparticles was significantly decrease blood glucose levels and increase body weight. Hence, it can be concluded that oral insulin supplementation with nano particles may have significant effect on hyperglycemic controls.
Oral Delivery of Insulin Loaded into Polymeric Nanoparticles in Rats
Drug Delivery Letters, 2011
Diabetes prevalence is steadily increasing and both type 1 and type 2 contribute to this "diabetes epidemic". Insulin is the sole therapeutic, life-saving option for type 1 diabetes with patients self-injecting the hormone every day for life. In this study, insulin has been loaded into polymeric nanoparticles (Np) of poly (D,L-lactide-co-glycolide) and different amounts of insulin-loaded Np (1, 3 or 10 I.U./kg) were administered by oral gavage to normal and diabetic rats, s.c. pre-treated with omeprazole (5 mg/Kg). In normal rats, the in vivo results highlighted a dose-related decrease of blood glucose levels in normal rats at the end of the observation period (20-50% depending on the doses of insulin delivered by Np). In diabetic rats, the dose of 3 I.U./kg produced a 50% decrease of the glycaemia 90 min after the treatment, with an effect stable up to the end of the observation period; a higher dose of insulin delivered by Np (10 I.U./kg) developed a significant decrease of glycaemia (65%). Correspondently, in diabetic rats, plasma insulin levels increased in a doserelated manner (3, 5, and 7-folds with respect to the basal level, depending on insulin doses delivered by NPs) with still significant values 2 h after administration. Thus, these Np are able, after pre-treatment with omeprazole, to transport insulin across the intestinal barrier, preserving the biological activity of the hormone in rats and if replicated in humans, it could suggest the concrete possibility of oral administration of insulin.
In Vitro Simulation of in Vivo Performance of Oral Dosed Nanoparticulate Insulin
2013
This dissertation would not have been possible without the help and support of so many people in so many ways. I would like first and foremost extend my appreciation to my supervisor, Dr. Ronald Neufeld, for his guidance, support and patience throughout this project. Thank you for encouraging me to grow and develop both professionally and personally that allows me to be a better informed and more effective person in my future professional life. Thank you for teaching me how to approach research with an open mind and for your insightful discussions, advice and tireless editing. Thanks to my lab mates, Michael Hyrnyk and Vitaliy Kapishon for sharing their knowledge, experiences and creativity. I would like to offer my sincere gratitude to my wonderful family, especially my Mom, Dad and my lovely brother Danial, who are always my sources of strength and motivation. Although we are apart 1000s of kilometers but our hearts are close and your inspiration and constant encouragement always support me in every aspect of my life. Thank you for always believing in me and my abilities and thanks for supporting me in every step of my life. Finally I would like to express my deepest thanks to my gorgeous husband Ahmad, who always puts smile on my face and gives me his love. Thank you so much for all of your endless encouragement, love, advice and emotional support that fueled my interest during my studies and our personal life. Thank you for being with me in every step of the way. I also want to thank my in-laws, Rezvan and M.Reza for their unconditional support.
Extensive research has been carried out to explore the potential ways of orally delivering insulin for the treatment of diabetes. Advancements in nanotechnology have brought the scientific community ever closer to this goal. The current review focuses on the various barriers existing in the route of oral insulin delivery and the strategies undertaken so far to overcome those by harnessing nanoparticles as potential vehicles of insulin. Additionally, an overview on the performance of various nanoparticle formulations including polymeric as well as lipid-based preparations will be given in context to their levels of success for insulin delivery through the intestinal epithelium. Finally, future prospects on nano-insulin therapy will be discussed.