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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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Abstract

Purpose

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.

Conclusion

Formulation with the PGC excipient offers a viable alternative to biochemically changing insulin or other receptor binding peptides to improve PD properties.

Blood glucose development in STZ-diabetic Sprague Dawley rats after s.c. injection of 1 mg/kg regular human insulin formulated with formulations 605c, 421a, and 421b, or an equivalent dose of insulin glargine.

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Abbreviations

BG:

blood glucose

NPH:

Neutral Protamine Hagedorn insulin

PGC:

Protected graft copolymer

STZ:

streptozotocin

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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.

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Authors and Affiliations

  1. PharmaIN Corporation, 720 Broadway, Seattle, Washington, 98122, USA

    Sandra Reichstetter, Gerardo M. Castillo, ManShun Lai, Akiko Nishimoto-Ashfield & Elijah M. Bolotin

  2. Toxicology Research Laboratory, Department of Pharmacology College of Medicine, University of Illinois at Chicago, 808 South Wood Street, Room 1306, Chicago, Illinois, 60612, USA

    Aryamitra Banerjee & Alexander V. Lyubimov

  3. University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Alexei Bogdanov

Authors
  1. Sandra Reichstetter
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  2. Gerardo M. Castillo
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  3. ManShun Lai
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  4. Akiko Nishimoto-Ashfield
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  5. Aryamitra Banerjee
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  6. Alexei Bogdanov
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  7. Alexander V. Lyubimov
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  8. Elijah M. Bolotin
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Correspondence to Sandra Reichstetter or Elijah M. Bolotin.

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Reichstetter, S., Castillo, G.M., Lai, M. et al. Protected Graft Copolymer (PGC) Basal Formulation of Insulin as Potentially Safer Alternative to Lantus® (Insulin-Glargine): A Streptozotocin-Induced, Diabetic Sprague Dawley Rats Study. Pharm Res 29, 1033–1039 (2012). https://doi.org/10.1007/s11095-011-0646-8

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  • DOI: https://doi.org/10.1007/s11095-011-0646-8

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