Examples of PK/PD Results Using PGC with a Variety of Peptides and Proteins
PGC extends half-life of both ANP and BNP in murine model
PGC extends dosing interval and efficacy of GLP-1
Subcutaneous 1 mg/kg, n=10
Similar effect on HbA1c with far fewer injections
After 7 weeks of treatment
PGC modulates acute side-effects of bolus injection (VIP)
PGC prevents the severe drop in blood pressure (side effect of VIP) due to larger PGC size targeting mainly to endothelium vs. smooth muscle
PGC-HBEGF plus oral Omeprazole given once a day reverses MLDS diabetes
Subcutaneous HB-EGF PK (n=3, BALB/c mice). PGC was loaded 0.5% w/w with HBEGF, mice were dosed at 300 μg/kg HBEGF.
PGC improves efficacy in type 1 diabetes
Multiple Low Dose Streptozotocin Diabetic Mice model: Five consecutive days of Streptozotocin to induce diabetes, then followed by 28-day treatments. (n=10) Gr 1: Saline non-diabetic control Gr 2: Saline diabetic control Gr 3: HBEGF once a day (0.3 mg/Kg) Gr 5: Omeprazole (50 mg/Kg Gr 6: Omeprazole (50 mg/Kg) and PGC-HBEGF (0.3 mg/Kg at 0.5% loading) once a day.
Larger Proteins (Leptin) can also bind to PGC for extended bioavailability
Subcutaneous Leptin PK (n=5, Sprague-Dawley rats). PGC was loaded 2% w/w with Leptin; Rats were dosed at 1 mg/kg Leptin.
A. Computer-generated model of PGC fragment with MPEG protective chain and hydrophobic elements represented by fatty acid residues.
B. A computer simulated representation of a leptin molecule binding to the hydrophobic “core” of PGC.
PGC extends FGF4 and FGF7 bioavailability and mitigates the lethality of partial body irradiation injury
FGF (Fibroblast growth factor) 7
Subcutaneous FGF 7 PK (n=3, CD-1 mice). PGC was loaded 5% w/w with FGF 7, mice were dosed at 0.6 mg/kg FGF 7.
Kaplan-Meier Survival curves, GI irradiated with 15.7 Gy (LD50/30)
24 hours after irradiation mice were treated daily with SC injections for 7 days; C57BL/6J mice, n=30.
Amifostine is a pretreatment control
PF4=PGC-FGF4 (3 mg/Kg); PF7=PGC-FGF7 (3 mg/Kg)