Use of natural plant exudates (Sanguis Draxonis) for sustained oral insulin delivery with dramatic reduction of glycemic effects in diabetic rats.

Sanguis Draxonis (SD), a kind of natural plant exudates, has been prescribed for handling diabetic disorders as a Chinese traditional herb. Surprisingly, SD was found to be a good material for oral insulin delivery. The Insulin-loaded Sanguis Draxonis nanocapsules (ISDN) were prepared by deposition technique. The average size and width of distribution of ISDN were 184+/-24 and 110+/-16 nm, respectively. The insulin encapsulation efficiency of ISDN reached up to 69.6+/-5.6%. In vitro the release profile of insulin from ISDN can be well modeled using an exponential function [Y=1-exp(-0.0275t)], showing that there was no initial burst release of insulin. The stability studies indicated that the majority of initial amount of insulin in ISDN was preserved not only after incubation of ISDN in three kinds of proteolytic enzyme solutions at 37 degrees C for 30 min, but also after its storage at 25 degrees C for 6 months. After a single oral administration of ISDN at the dose of 25, 50, and 75 IU/kg in STZ-induced diabetic rats, the blood glucose level was depressed to 60.5+/-2.7%, 52.6+/-2.3% and 47.3+/-3.1% of the initial value at time point 8 h, respectively, and these marked decreases lasted 2-4 days. When 125I-labeled ISDN was administered orally, the distribution sequence of isotope intensity of 125I radioactivity in rat organs was as follows: liver, kidney, heart, spleen and lung. In addition, 125I radioactivity disappeared progressively as a function of time, parallel to the biological effect. In conclusion, the results demonstrate that ISDN elicits a long-term hypoglycemic effect significantly after oral administration in STZ-induced diabetic rats and it can be considered as a stable and effective system for oral insulin delivery.