Figure 3: Silica nanoparticles enabled oral protein delivery in healthy mice.

(a) Two hours following oral gavage of silica particles to mice, an intestinal injection of 1 U/kg insulin induced sustained reductions in blood glucose levels. Polystyrene nanoparticles did not enable insulin absorption. A 1 U/kg subcutaneous insulin dose induced a pronounced but brief response. (b) Integrated areas above the curves (AACs) from (a) show that oral delivery with silica nanoparticles and subcutaneous injection resulted in comparable total pharmacodynamic effect. Blood glucose levels and areas above the curves were (c, d) particle dose dependent with a constant insulin dose of 1 U/kg and (e, f) insulin dose dependent with a constant particle dose of 100 mg/kg. (g) Pharmacokinetically, subcutaneous injection caused a spike in blood insulin concentration followed by a rapid decline. By contrast, intestinal administration after silica nanoparticles sustained more modest elevations in serum levels over several hours, leading to (h) nearly equal areas under the blood insulin curves for the two administration methods. (i) Orally delivered insulin induced pronounced and sustained hypoglycaemia at doses as low as 10 U/kg when administered to silica-treated mice. Oral insulin without particles produced no effect compared to the control protein BSA. (j) Particle treatments resulted in multiple-fold increases in the area above the blood glucose curve calculated to 10 hours. (k) Particle treatments enabled systemic uptake of exenatide administered orally in capsules (1 mg/kg), leading to (l) a substantially higher area under the serum concentration curve when compared to capsules administered without silica. Statistics bars display arithmetic mean and s.e.m. for biological replicates (n = 5). * p < 0.05 w.r.t. control by one-tailed t-test. # p < 0.05 by one-way ANOVA.