In Vitro and in Vivo Comparative Study of Oral Nanoparticles and Gut Iontophoresis as Oral Delivery Systems for Insulin
Multiple daily injections of insulin for diabetes cause many hazards for diabetic patients. Oral noninvasive insulin delivery could be more convenient and less painful than parenteral route. In past decades transdermal iontophoresis had been studied for insulin delivery across the skin with or witho...
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| Published in: | Biological & pharmaceutical bulletin Vol. 44; no. 2; pp. 251 - 258 |
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| Abstract | Multiple daily injections of insulin for diabetes cause many hazards for diabetic patients. Oral noninvasive insulin delivery could be more convenient and less painful than parenteral route. In past decades transdermal iontophoresis had been studied for insulin delivery across the skin with or without chemical permeation enhancers. However, the results of these studies were not efficacious and serum insulin levels were not therapeutically effective. In the present study an advanced technology “gut iontophoresis” for insulin delivery across the gut wall was compared with traditional oral insulin delivery in the form of nanoparticles. In vitro application of electric current to the intestinal membrane could enhance the flux of insulin nanoparticles (3.4 fold enhancement of insulin transport) from the donor to the receptor compartment in the Franz cell. In vivo iontophoresis of insulin nanoparticles through the gut wall would produce intense hypoglycemia (57% glycemia drop in 3 h) without damage of the intestinal tissues. Cell viability assay indicated that 50–500 µg/mL nanoparticles had no toxic effect on Caco-2 cells. Nanoparticles gut iontophoresis could be a promising non-invasive technique for oral insulin delivery. |
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| AbstractList | Multiple daily injections of insulin for diabetes cause many hazards for diabetic patients. Oral noninvasive insulin delivery could be more convenient and less painful than parenteral route. In past decades transdermal iontophoresis had been studied for insulin delivery across the skin with or without chemical permeation enhancers. However, the results of these studies were not efficacious and serum insulin levels were not therapeutically effective. In the present study an advanced technology "gut iontophoresis" for insulin delivery across the gut wall was compared with traditional oral insulin delivery in the form of nanoparticles. In vitro application of electric current to the intestinal membrane could enhance the flux of insulin nanoparticles (3.4 fold enhancement of insulin transport) from the donor to the receptor compartment in the Franz cell. In vivo iontophoresis of insulin nanoparticles through the gut wall would produce intense hypoglycemia (57% glycemia drop in 3 h) without damage of the intestinal tissues. Cell viability assay indicated that 50-500 µg/mL nanoparticles had no toxic effect on Caco-2 cells. Nanoparticles gut iontophoresis could be a promising non-invasive technique for oral insulin delivery. Multiple daily injections of insulin for diabetes cause many hazards for diabetic patients. Oral noninvasive insulin delivery could be more convenient and less painful than parenteral route. In past decades transdermal iontophoresis had been studied for insulin delivery across the skin with or without chemical permeation enhancers. However, the results of these studies were not efficacious and serum insulin levels were not therapeutically effective. In the present study an advanced technology “gut iontophoresis” for insulin delivery across the gut wall was compared with traditional oral insulin delivery in the form of nanoparticles. In vitro application of electric current to the intestinal membrane could enhance the flux of insulin nanoparticles (3.4 fold enhancement of insulin transport) from the donor to the receptor compartment in the Franz cell. In vivo iontophoresis of insulin nanoparticles through the gut wall would produce intense hypoglycemia (57% glycemia drop in 3 h) without damage of the intestinal tissues. Cell viability assay indicated that 50–500 µg/mL nanoparticles had no toxic effect on Caco-2 cells. Nanoparticles gut iontophoresis could be a promising non-invasive technique for oral insulin delivery. Graphical Abstract |
| Author | Ali, Amir I. Elkhatib, Mona M. Al-badrawy, Ali S. |
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| Cites_doi | 10.1208/s12249-012-9807-2 10.1023/B:PHAM.0000029282.44140.2e 10.1016/j.ijbiomac.2014.05.036 10.1016/j.sna.2011.05.024 10.5402/2011/780150 10.1016/j.colsurfb.2011.11.016 10.21577/0100-4042.20160159 10.1016/j.addr.2017.11.003 10.1016/j.jconrel.2006.10.023 10.3109/02652048.2011.638992 10.1016/S0168-3659(99)00285-0 10.3390/pharmaceutics10040214 10.1016/j.ejpb.2004.10.006 10.1016/S0378-5173(03)00034-6 10.1016/j.jsps.2012.02.001 10.1016/j.ijpharm.2010.04.006 10.3390/nano9081081 10.1016/S2222-1808(14)60590-9 10.1007/s11095-007-9367-4 10.1159/000081114 10.3390/ijms17071171 10.1016/0169-409X(92)90024-K |
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| SubjectTerms | Blood glucose Cell viability Diabetes mellitus Digestive system Gastrointestinal tract gut iontophoresis Hypoglycemia Insulin Intestine Iontophoresis nanoparticle Nanoparticles oral delivery |
| Title | In Vitro and in Vivo Comparative Study of Oral Nanoparticles and Gut Iontophoresis as Oral Delivery Systems for Insulin |
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