Protected graft copolymer (PGC) basal formulation of insulin as potentially safer alternative to Lantus(R) (insulin-glargine): a streptozotocin-induced, diabetic Sprague Dawley rats study
Department of Radiology
Animals; Blood Glucose; Chemistry, Pharmaceutical; Diabetes Mellitus, Experimental; Drug Carriers; Excipients; Humans; Hypoglycemic Agents; Insulin, Long-Acting; Male; Polymers; Rats; Rats, Sprague-Dawley; Receptor, IGF Type 1
Hormones, Hormone Substitutes, and Hormone Antagonists | Medicinal and Pharmaceutical Chemistry | Medicinal Chemistry and Pharmaceutics | Pharmaceutics and Drug Design | Radiology | Therapeutics
PURPOSE: To develop a long-acting formulation of native human insulin with a similar pharmacodynamics (PD) profile as the insulin analogue insulin glargine (Lantus(R), 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: Formulation with the PGC excipient offers a viable alternative to biochemically changing insulin or other receptor binding peptides to improve PD properties.
DOI of Published Version
Pharm Res. 2012 Apr;29(4):1033-9. doi: 10.1007/s11095-011-0646-8. Epub 2011 Dec 28. Link to article on publisher's site
Reichstetter, Sandra; Castillo, Gerardo M.; Lai, ManShun; Nishimoto-Ashfield, Akiko; Banerjee, Aryamitra; Bogdanov, Alexei A. Jr.; Lyubimov, Alexander V.; and Bolotin, Elijah M., "Protected graft copolymer (PGC) basal formulation of insulin as potentially safer alternative to Lantus(R) (insulin-glargine): a streptozotocin-induced, diabetic Sprague Dawley rats study" (2012). Radiology Publications and Presentations. 85.