Penetratin derivative-based nanocomplexes for enhanced intestinal insulin delivery

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Nanotechnology

Background:

• Intestinal insulin delivery is hindered by insufficient mucosal permeability.
• Cell-penetrating peptides (CPPs) offer potential for enhanced drug permeation.
• Optimizing CPPs is crucial for effective oral insulin formulations.

Purpose of the Study:

• To develop and evaluate CPP-based nanocomplexes for improved insulin mucosal permeation.
• To investigate the efficacy of a modified CPP, P-bis-CD, for intestinal insulin delivery.
• To assess the safety and bioavailability of P-bis-CD nanocomplexes.

Main Methods:

• Site-specific modification of Penetratin with bis-β-cyclodextrin (P-bis-CD).
• Preparation of insulin-loaded nanocomplexes using P-bis-CD and Penetratin.
• In vitro and in situ permeation studies.
• In vivo hypoglycemic effect and pharmacokinetic studies in diabetic rats.
• Toxicity assessment of P-bis-CD nanocomplexes.

Main Results:

• P-bis-CD nanocomplexes exhibited enhanced stability and stronger intermolecular interactions compared to Penetratin nanocomplexes.
• Significantly improved insulin permeation in vitro and in situ with P-bis-CD nanocomplexes.
• P-bis-CD nanocomplexes demonstrated a notable hypoglycemic effect in diabetic rats, lasting 6 hours.
• Relative pharmacological availability and bioavailability were 3.0-fold and 2.3-fold higher, respectively, for P-bis-CD nanocomplexes.
• No toxicity observed after 7 days of P-bis-CD nanocomplex administration.

Conclusions:

• P-bis-CD is a promising permeation enhancer for intestinal insulin delivery.
• Chemical modification of CPPs is a viable strategy to improve their therapeutic potential.
• P-bis-CD nanocomplexes represent a safe and effective approach for oral insulin delivery.