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Using protease inhibitors to improve protein stability in the presence of skin: A case study on the stability of insulin like growth factor 1 by S. Dubey; R. Perozzo; L. Scapozza; Y.N. Kalia is a Pharmacology, Toxicology and Pharmaceutics article available to read on EtoBox.

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Insulin-like growth factor 1 (IGF-1) is indicated for growth failure in pediatric patients with primary IGF-1 deficiency and for patients with neutralizing antibodies to growth hormone. IGF-1 was cloned, expressed and purified in-house. Preliminary stability studies prior to the transdermal delivery experiments showed that although stable in contact with stratum corneum, the solution concentration of IGF-1 decreased to 23.63 ± 2.48 and 21.58 ± 2.62% of the initial value upon exposure for 8 h to porcine dermis of 250 and 750 μm thickness. This led to an investigation into how it might be possible to improve the stability of IGF-1 in the presence of porcine/human skin. The stability of IGF-1 in the presence of dermis improved upon heating the skin samples at 60 °C for 2 min suggesting that IGF-1 was subject to enzymatic degradation. Although addition of the protease inhibitor, phenylmethanesulfonyl fluoride (PMSF) alone, did not improve stability, the use of a protease inhibitor cocktail completely blocked proteolytic degradation of IGF-1; the solution concentration after an 8 h exposure to porcine skin was equivalent to the initial level (103.87 ± 9.15%). The results obtained with p

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Author

S. Dubey; R. Perozzo; L. Scapozza; Y.N. Kalia

Publisher

Elsevier BV

Published

2020

Language

EN

Field

Pharmacology, Toxicology and Pharmaceutics (Life Sciences)