Difference between revisions of "Part:BBa K1074000"

Figure 1 Systemic protein drug delivery mediated by TD-1. (a) 125I-Insulin delivery. 125I -insulin (5,000,000 c.p.m.) was topically coadministered to normalrats with various amounts of TD-1. Radioactivity in the whole blood samples was measured at various time points after administration. (b,c) Delivery of therapeutic levels of insulin. Streptozotocin-induced diabetic rats were topically administered as shown, with the following dosing: TD-1, 500 mg; AP-1, 500 mg ; SLA/PP, 0.5% (wt/vol); porcine insulin, 70 mg, with the exception of subcutaneous treatment (14 mg). At various time points after administration, serum insulin concentration (b) and blood glucose level (c) were measured. Glucose levels were normalized against the initial (0 h) value. Mean ± s.e.m. (n ¼ 6 for glucose and n Z 3 for insulin). *P o 0.05, **P o 0.01, ***P o 0.001. (d,e) Dose-response of TD-1. Porcine insulin (70 mg) and various doses of TD-1 were topically coadministered to streptozotocin-induced diabetic rats. Serum insulin (d) and blood glucose (e) levels were measured before and 5 h after administration. Mean ± s.e.m. (n ¼ 6 for glucose and n Z 3 for insulin). (f) Transdermal delivery of human growth hormone. 500 mg of recombinant human growth hormone (495% pure) was topically coadministered to dexamethasone-treated rats with AP-1, two different doses of TD-1, or saline as indicated. At various time points after administration, serum growth hormone levels were measured. Mean ± s.e.m. (n Z 3) *P o 0.05.

figure 2 Transdermal activity of TD-1 peptide variants

figure 3 Exploring TD-1’s mode of action. (a) TD-1 does not bind insulin directly. 125I-insulin was added to ELISA microwell plates precoated with increasing amounts of TD-1 (left panel) or an insulin antibody (right panel), and bound radioactivity was determined after washing. (b) Delivery of different molecular forms of insulin by TD-1. 500 mg of TD-1 and 200 mg of insulin were administered to the abdominal skin of streptozotocin-induced diabetic rats in 100 ml saline (after adjusting the pH to 2.0, 3.0 and 7.0, respectively), and serum insulin was measured before and 5 h after administration. (c,d) Timelapse effect of TD-1. TD-1 (500 mg) in 100 ml of saline was administered to the abdominal skin of streptozotocin-induced diabetic rats and left for 5 min. The skin area was then carefully washed with an excess of saline. After various waiting periods, porcine insulin (70 mg in 100 ml saline) was administered to the same skin site. Serum insulin (c) and blood glucose (d) levels were measured before TD-1 treatment and 5 h after insulin administration. Coadministration (CO) of TD-1 (500 mg) and insulin (70 mg) served as the control. Mean ± s.e.m., (n ¼ 6 for glucose and n Z 3 for insulin).