Diabetes correction in pancreatectomized canines by orally absorbable insulin-deoxycholate complex

Area of Science:

• Biochemistry
• Pharmacology
• Drug Delivery Systems

Background:

• Conventional insulin therapy requires injections, posing challenges for patient adherence and mimicking physiological insulin release.
• Developing an oral insulin formulation is highly desirable for diabetic patients to improve treatment convenience and efficacy.

Purpose of the Study:

• To evaluate the characteristics of an insulin/deoxycholate-based synthetic complex (insulin/DCK).
• To assess the efficacy of oral insulin/DCK administration in correcting diabetes in pancreatectomized canines.

Main Methods:

• In vitro evaluation of insulin/DCK complexation, including structural integrity, digestive enzyme stability, lipophilicity, and Caco-2 cell permeability.
• In vivo studies in diabetic canines involving oral administration of insulin/DCK via Eudragit-coated capsules.
• Assessment of glucodynamics, pharmacokinetics, oral glucose tolerance tests (OGTT), and reproducibility of therapeutic effects.

Main Results:

• Insulin/DCK complexation enhanced insulin's stability against digestive enzymes and significantly increased its lipophilicity and permeability.
• Oral administration of insulin/DCK in diabetic canines dose-dependently reduced plasma glucose levels (28-67%) and increased plasma insulin.
• Insulin/DCK maintained normoglycemia during OGTT and demonstrated reproducible therapeutic efficacy over 3 days.

Conclusions:

• The insulin/DCK complex offers enhanced digestive enzyme resistance and improved permeability for effective oral insulin delivery.
• This deoxycholate-based formulation provides intact insulin without chemical modification, demonstrating potential as an oral therapeutic alternative to injectable insulin.