Protected graft copolymer (PGC) basal formulation of insulin as potentially safer alternative to Lantus® (insulin-glargine): a streptozotocin-induced, diabetic Sprague Dawley rats study.
OBJECTIVE
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.


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.


CONCLUSIONS
Formulation with the PGC excipient offers a viable alternative to biochemically changing insulin or other receptor binding peptides to improve PD properties.
PharmaIN Corporation, 720 Broadway, Seattle, Washington 98122, USA. sreichstetter@pharmain.com
Sandra
S
Reichstetter
Gerardo M
GM
Castillo
ManShun
M
Lai
Akiko
A
Nishimoto-Ashfield
Aryamitra
A
Banerjee
Alexei
A
Bogdanov
Alexander V
AV
Lyubimov
Elijah M
EM
Bolotin
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000008:administration & dosage* / Q000737:chemistry*; D008297:Male; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000378:metabolism
D001786:Blood Glucose; D004337:Drug Carriers; D005079:Excipients; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D011108:Polymers; D000069036:Insulin Glargine; D017526:Receptor, IGF Type 1