Protected Graft Copolymer (PGC) Basal Formulation of Insulin as Potentially Safer Alternative to Lantus® (Insulin-Glargine): A Streptozotocin-Induced, Diabetic Sprague Dawley Rats Study
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To develop a long-acting formulation of native human insulin with a similar pharmacodynamics (PD) profile as the insulin analogue insulin glargine (Lantus®, Sanofi-Aventis) with the expectation of retaining native human insulin’s superior safety profile as insulin glargine is able to activate the insulin-like growth factor 1 (IGF-1) receptor and is linked to a number of malignancies at a higher rate than regular human insulin.
Development of protected graft copolymer (PGC) excipients that bind native human insulin non-covalently and testing blood glucose control obtained with these formulations in streptozotocin-induced diabetic Sprague Dawley rats compared to equally dosed insulin glargine.
PGC-formulations of native human insulin are able to control blood glucose to the same extent and for the same amount of time after s.c. injection as the insulin analogue insulin glargine. No biochemical changes were made to the insulin that would change receptor binding and activation with their possible negative effects on the safety of the insulin.
Formulation with the PGC excipient offers a viable alternative to biochemically changing insulin or other receptor binding peptides to improve PD properties.
KEY WORDSbasal drug delivery excipient human insulin long-acting nanocarrier peptide PGC protected graft copolymer
Neutral Protamine Hagedorn insulin
Protected graft copolymer
Acknowledgements & Disclosures
The work described in this publication has been supported by the NIH/NIDDK SBIR grant 5R44 DK069727-04 and 3R44DK069727-04S1. We also thank Ms. Cynthia C. Jones for expert help in editing and proof reading the manuscript.
Sandra Reichstetter, Man Shun Lai, Akiko Nishimoto-Ashfield, Gerardo Castillo, and Elijah Bolotin are paid employees and stock option holders of PharmaIN Corporation. Alexei Bogdanov is a shareholder of PharmaIN Corporation.