Delivery of Fenofibrate to Ocular Tissues using 2-Hydroxypropyl-β-cyclodextrin-Based Micelles

Area of Science:

• Ocular Drug Delivery
• Nanotechnology in Medicine
• Pharmaceutical Sciences

Background:

• Age-related macular degeneration and diabetic retinopathy cause significant vision impairment.
• Current intravitreal injections for these conditions have side effects; topical delivery is preferred but hindered by ocular barriers.
• Fenofibrate (FEB), a poorly water-soluble drug, requires enhanced delivery systems for ocular application.

Purpose of the Study:

• To prepare and characterize poly(pseudo)rotaxanes (PPRs) using 2-hydroxypropyl-β-cyclodextrin (2-HPβCD), Pluronic® F127 (PF127), and Soluplus®.
• To enhance the solubility and ocular permeation of fenofibrate (FEB) for potential eye disease treatment.
• To investigate the drug encapsulation, solubility enhancement mechanisms, and permeation kinetics.

Main Methods:

• Preparation and characterization of FEB-loaded micelles and PPRs using Dynamic Light Scattering (DLS), ¹H Nuclear Magnetic Resonance (NMR), and X-ray Diffraction (XRD).
• Evaluation of FEB solubility enhancement in prepared formulations.
• Ex vivo permeation studies across porcine scleral tissue and mathematical modeling using Fick's law.

Main Results:

• FEB was successfully encapsulated into micelles and PPRs with small particle sizes (7-67 nm).
• A 910-fold increase in FEB solubility was achieved with 2-HPβCD addition, demonstrating a synergistic effect.
• FEB-loaded PPRs facilitated FEB permeation across scleral tissue, with permeation levels ranging from 0.27 to 4.25 μg/cm².

Conclusions:

• Poly(pseudo)rotaxanes (PPRs) show significant potential as an effective drug delivery system for ocular applications.
• The synergistic effect of 2-HPβCD greatly enhances the solubility of poorly water-soluble drugs like FEB.
• Mathematical modeling is crucial for understanding drug permeation mechanisms in ocular tissues.