Stabilization of bovine insulin against agitation-induced aggregation using RNA aptamers.

作者: Ravinder Malik , Ipsita Roy

DOI: 10.1016/J.IJPHARM.2013.05.004

关键词:

摘要: Abstract Stabilization of monomeric insulin is a primary requirement for preserving the efficacy final formulation. Degraded and/or aggregated protein as well presence any conventional excipients can result in immunogenic or anaphylactic reactions, and reduced bioavailability drug. The aim this work was to select novel RNA-based stabilizers bovine which would recognize bind help retain its bioactivity. RNA aptamers were selected by an vitro selection method. They screened their ability inhibit fibrillation using agitation stress condition. activity determined phosphorylation downstream proteins cell. In vivo bioactivity diabetic rat model. aptamers, bound with very low dissociation constants high specificity, selected. These sequences aligned consensus regions found. had no effect on signalling cascade initiated insulin. insulin, measured lower plasma glucose level model, also remained unchanged. are class have disrupt protein–protein interactions hence aggregation. Their non-toxic non-immunogenic nature makes such formulations safe use.

参考文章(50)
Allison G. Hoffman, Sarah E. Schram, Nacide G. Ercan-Fang, Erin M. Warshaw, Type I allergy to insulin: case report and review of localized and systemic reactions to insulin. Dermatitis. ,vol. 19, pp. 52- 58 ,(2008) , 10.2310/6620.2008.06054
A. Krishna. Mallia, Greg T. Hermanson, Paul K. Smith, Immobilized Affinity Ligand Techniques ,(1992)
D. Rickwood, B. D. Hames, Gel electrophoresis of proteins: a practical approach : IRL. ,(1981)
Howard A Wolpert, Raquel N Faradji, Susan Bonner-Weir, Myra A Lipes, Metabolic decompensation in pump users due to lispro insulin precipitation BMJ. ,vol. 324, pp. 1253- 1253 ,(2002) , 10.1136/BMJ.324.7348.1253
S. Edwin Fineberg, Thomas T. Kawabata, Deborah Finco-Kent, Robert J. Fountaine, Gregory L. Finch, Alan S. Krasner, Immunological responses to exogenous insulin. Endocrine Reviews. ,vol. 28, pp. 625- 652 ,(2007) , 10.1210/ER.2007-0002
Daniel Steinmann, J. Andrea Ji, Y. John Wang, Christian Schöneich, Oxidation of human growth hormone by oxygen-centered radicals: formation of Leu-101 hydroperoxide and Tyr-103 oxidation products. Molecular Pharmaceutics. ,vol. 9, pp. 803- 814 ,(2012) , 10.1021/MP3001028
Liza Nielsen, Sven Frokjaer, John F. Carpenter, Jens Brange, Studies of the structure of insulin fibrils by Fourier transform infrared (FTIR) spectroscopy and electron microscopy. Journal of Pharmaceutical Sciences. ,vol. 90, pp. 29- 37 ,(2001) , 10.1002/1520-6017(200101)90:1<29::AID-JPS4>3.0.CO;2-4
J. M. Brostoff, H. Keen, J. Brostoff, A diabetic life before and after the insulin era. Diabetologia. ,vol. 50, pp. 1351- 1353 ,(2007) , 10.1007/S00125-007-0641-0
Ravinder Malik, Ipsita Roy, Probing the mechanism of insulin aggregation during agitation International Journal of Pharmaceutics. ,vol. 413, pp. 73- 80 ,(2011) , 10.1016/J.IJPHARM.2011.04.024
Sean M. Switzer, Emily G. Moser, Briana E. Rockler, Satish K. Garg, Intensive Insulin Therapy in Patients with Type 1 Diabetes Mellitus Endocrinology and Metabolism Clinics of North America. ,vol. 41, pp. 89- 104 ,(2012) , 10.1016/J.ECL.2011.12.001