Cell-penetrating peptide enhanced insulin buccal absorption.

Area of Science:

• Biotechnology
• Drug Delivery
• Nanomedicine

Background:

• Non-injectable delivery of large, hydrophilic molecules like peptides and proteins faces significant challenges, including gastrointestinal degradation and poor absorption.
• Buccal delivery of insulin is hindered by low efficacy and potential mucosal irritation, necessitating innovative strategies.

Purpose of the Study:

• To develop and evaluate a novel protein delivery strategy using a conjugate of cell-penetrating peptides and insulin for enhanced buccal delivery.
• To overcome the limitations of conventional insulin delivery methods, aiming for improved bioavailability and reduced side effects.

Main Methods:

• Preparation of an insulin-PEG-cell-penetrating peptide conjugate (INS-PEG-LMWP).
• In vitro assessment of INS-PEG-LMWP transport across buccal mucosal models.
• In vivo characterization of bioactivity, hypoglycaemic effect, and safety profile of the conjugate.

Main Results:

• In vitro studies showed significantly increased uptake and transport of INS-PEG-LMWP across buccal mucosal multilayers.
• The conjugate's delivery mechanism appears to be energy-independent and involves electrostatic adsorption.
• INS-PEG-LMWP exhibited high relative pharmacological bioavailability (up to 26.86%) with no observable mucosal irritation.

Conclusions:

• Cell-penetrating peptides represent a promising tool for enhancing the permeability of insulin across epithelial barriers in buccal delivery.
• The developed INS-PEG-LMWP conjugate offers a viable, non-injectable alternative for insulin administration with improved efficacy and safety.