TY - JOUR
T1 - Novel fibrillar insulin formulations for oral administration
T2 - Formulation and in vivo studies in diabetic mice
AU - Dekel, Y.
AU - Glucksam, Y.
AU - Margalit, R.
PY - 2010/4
Y1 - 2010/4
N2 - The advantages of oral insulin are well-recognized, yet such formulations are still unavailable. Towards that goal we developed, and evaluated in diabetic ICR mice, two novel insulin microparticles for oral delivery. Although different in structure and shape, both microparticle formulations share: (i) hyaluronan on their surface (ii) fibrillar insulin, loaded at 50-100% efficiency over the insulin range of 1-10. mg/ml and (iii) high retention of insulin loads in simulated gastro-intestinal environments. BGL values in diabetic ICR mice were tested over a time span of 8. h, following a single oral dose of each formulation, using two protocols: the conventional (12. h pre-fasting and 8. h fasting); our revised protocol (no pre-fasting, meal at t=4. h). In both protocols, initial blood glucose levels (BGL) were 400-600. mg/dL and the novel formulations generated a continuous reduction of BGL. Results in the revised protocol, that mimics human eating habits, were more pronounced, providing stable (over several hours) glucose reductions approaching non-diabetic BGL values. These two fibrillar insulin formulations, and the fibrillar form for therapeutic proteins, merit further studies.
AB - The advantages of oral insulin are well-recognized, yet such formulations are still unavailable. Towards that goal we developed, and evaluated in diabetic ICR mice, two novel insulin microparticles for oral delivery. Although different in structure and shape, both microparticle formulations share: (i) hyaluronan on their surface (ii) fibrillar insulin, loaded at 50-100% efficiency over the insulin range of 1-10. mg/ml and (iii) high retention of insulin loads in simulated gastro-intestinal environments. BGL values in diabetic ICR mice were tested over a time span of 8. h, following a single oral dose of each formulation, using two protocols: the conventional (12. h pre-fasting and 8. h fasting); our revised protocol (no pre-fasting, meal at t=4. h). In both protocols, initial blood glucose levels (BGL) were 400-600. mg/dL and the novel formulations generated a continuous reduction of BGL. Results in the revised protocol, that mimics human eating habits, were more pronounced, providing stable (over several hours) glucose reductions approaching non-diabetic BGL values. These two fibrillar insulin formulations, and the fibrillar form for therapeutic proteins, merit further studies.
KW - Diabetes
KW - Drug delivery
KW - ICR mice
KW - Insulin fibrils
KW - Oral delivery
UR - http://www.scopus.com/inward/record.url?scp=77950519662&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2009.12.018
DO - 10.1016/j.jconrel.2009.12.018
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C2 - 20043960
AN - SCOPUS:77950519662
SN - 0168-3659
VL - 143
SP - 128
EP - 135
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 1
ER -