In the recent years, temperature and pH-sensitive hydrogels were developed as suitable carriers for drug delivery. In this study, four different pH-sensitive nanohydrogels were designed for an oral insulin delivery modeling. NIPAAm-MAA-HEM copolymers were synthesized by radical chain reaction with 80:8:12 ratios respectively. Reactions were carried out in four conditions including 1,4-dioxan and water as two distinct solution under nitrogen gas-flow. The copolymers were characterized with FT-IR, SEM and TEM. Copolymers were loaded with regular insulin by modified double emulsion method with ratio of 1:10. Release study carried out in pH 1.2 and pH 6.8 at 37 °C. For pH 6.8 and pH 1.2, 2 mg of the insulin loaded nanohydrogels was float in a beaker containing 100 mL of PBS with pH 6.8 and 100 mL of HCl solution with pH 1.2, respectively. Sample collection was done in different times and HPLC was used for analysis of samples using water/acetonitrile (65/35) as the mobile phase. Nanohydrogels synthesis reaction yield was 95 %, HPLC results showed that loading in 1,4-dioxan without cross-linker nanohydrogels was more than others, also indicated that the insulin release of 1,4-dioxan without cross-linker nanohydrogels at acidic pH is less, but in pH 6.8 is the most. Results showed that by opting suitable polymerization method and selecting the best nanohydrogels, we could obtain a suitable insulin loaded nanohydrogels for oral administration.
Background: This pilot study was designed to investigate the effect of orally delivered nanohydrogel insulin on serum glucose and insulin levels in patients with type 2 diabetes (T2DM). Methods: In this pilot before-after study, 8 T2DM patients received 300 IU insulin loaded nanohydrogel orally and the serum concentration of glucose and insulin were measured before treatment and consecutively during treatment. The area under the curve (AUC) was calculated for serum glucose and insulin and repeated measures of ANOVA, paired t-test were used for statistical analysis. Results: The changes in serum glucose level was not significant pretreatment (p=0.10) and during oral insulin treatment (p=0.71). Compared with pretreatment value, the serum glucose level was significantly lower in 7 A.M. (immediately after insulin therapy) and 8.30 A.M. during oral insulin treatment. The maximum reduction was observed 1.5 hours after insulin therapy and its effect lasted for more than 6 hours. The mean AUC of glucose was insignificantly decreased (p=0.16). The pretreatment (p=0.10) and during treatment (p=0.30) changes in serum insulin level were not statistically significant. The serum insulin level was increased significantly immediately after oral insulin therapy compared with pretreatment values. The mean AUC of insulin increased marginally significant (p=0.056). Conclusion: The results of the present pilot study showed that 300IU nanohydrogel oral insulin was effective in rapid lowering of serum glucose and its glucose lowering effect lasting for more than 6 hours. However, for any precise conclusions further studies with longer duration are needed.
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