Insulin Transdermal Delivery System for Diabetes Treatment Using a Biocompatible Ionic Liquid-Based Microemulsion

Area of Science:

• Materials Science
• Biotechnology
• Pharmaceutical Sciences

Background:

• Transdermal insulin delivery is crucial for diabetes management, offering a less invasive alternative to injections.
• The stratum corneum (SC) presents a significant barrier to transdermal drug permeation, particularly for large molecules like insulin.
• Developing effective non-invasive delivery systems requires overcoming the SC's robust barrier properties.

Purpose of the Study:

• To develop novel ionic liquid (IL)-in-oil microemulsion formulations (MEFs) for enhanced transdermal insulin delivery.
• To investigate the potential of biocompatible surface-active ILs (SAILs) based on choline-fatty acids ([Chl][FAs]) as key components in MEFs.
• To evaluate the efficacy, safety, and stability of these MEFs for transdermal insulin therapy.

Main Methods:

• Formulation of MEFs using [Chl][FAs] as surfactants, sorbitan monolaurate as a cosurfactant, choline propionate IL, and isopropyl myristate as the oil phase.
• Characterization of MEFs using ternary phase behavior, dynamic light scattering, and transmission electron microscopy to confirm thermodynamic stability and nanoparticle size.
• In vitro assessment of transdermal permeation enhancement and in vivo evaluation of blood glucose level reduction and pharmacokinetic profiles in diabetic mice.

Main Results:

• Thermodynamically stable MEFs with nanoparticle characteristics were successfully developed.
• MEFs significantly enhanced transdermal insulin permeation by disrupting the SC lipid lamellar structure via a fluidity-enhancing mechanism.
• In vivo studies in diabetic mice demonstrated significant blood glucose reduction, increased insulin bioavailability, and prolonged insulin circulation (half-life > 24 h) compared to subcutaneous injection.

Conclusions:

• SAIL-based MEFs represent a promising strategy for effective transdermal insulin delivery, offering a non-invasive and sustained therapeutic option.
• The developed MEFs are biocompatible, non-toxic, and exhibit good storage stability, making them suitable for practical applications.
• These findings suggest that SAIL-based MEFs could revolutionize insulin therapy and serve as a versatile nanocarrier for other protein and peptide drugs.