Transdermal delivery of nobiletin using ionic liquids

Area of Science:

• Pharmacology
• Materials Science
• Drug Delivery

Background:

• Nobiletin (NOB), a flavonoid, exhibits poor water solubility and oral bioavailability, limiting its therapeutic applications.
• Transdermal delivery offers a potential alternative route for administering NOB, bypassing first-pass metabolism and improving patient compliance.

Purpose of the Study:

• To investigate the feasibility of using choline and geranic acid (CAGE) for the transdermal delivery of NOB.
• To evaluate the solubility, transdermal absorption, and in vivo pharmacokinetic and pharmacodynamic properties of NOB formulated with CAGE.

Main Methods:

• Solubility studies were conducted to assess NOB solubility in CAGE.
• In vitro transdermal permeation tests were performed using Franz diffusion cells.
• In vivo pharmacokinetic studies measured NOB concentrations in plasma after transdermal and oral administration.
• Hypoglycemic effects were evaluated in rats administered NOB/CAGE.

Main Results:

• CAGE demonstrated excellent solubility enhancement for NOB through multipoint hydrogen bonding.
• In vitro tests confirmed CAGE's efficacy in enhancing NOB transdermal absorption compared to other enhancers.
• In vivo studies showed a 20-fold increase in NOB bioavailability with CAGE transdermal delivery versus oral administration.
• The NOB/CAGE formulation significantly reduced blood glucose levels in rats, indicating hypoglycemic activity.

Conclusions:

• Transdermal administration of NOB using CAGE is a feasible and highly effective delivery strategy.
• CAGE significantly improves NOB's solubility, permeability, and oral bioavailability.
• This CAGE-based transdermal system holds potential for other poorly soluble flavonoids with low permeability.