Development of Fast Penetrating Nano Eye Drop (FP-NED) With Long Lasting Residency Property

Abstract

Purpose : The innate ocular tissue barriers, microenvironment (osmolarity, pH, tear enzymes, etc.) and eye blinking make drug penetration and residency challenging that limit the drug bioavailability below 20% while rest of the drug washed away within 1-2 minutes. The presented technology provides an innovative approach to design a novel eye drop with fast corneal penetration and long-lasting residency in tear film.

Methods : Dexamethasone (DEXA) loaded liposomes (Phospholipon 90G: Cholesterol: Pluronic F-127 at 5.2: 1.26: 2.10 molar ratio) were prepared by thin film hydration method followed by blending with α-linoleic acid (1.6%, v/v) enriched microemulsion (PEG 400: Tween 80, 1:1 v/v ratio) to impart natural tear film microenvironment-like properties. The developed formulation was passed through high pressure homogenization at 20000 psi for 6 minutes (3 cycles) to achieve nano-scaled particulate system (Nano Eye Drops, NED). Short term stability (6 months) and in-use stability (4 weeks) studies were conducted. Cell toxicity, drug release, in-vivo biosafety and drug residence time in tear film were evaluated. Coumarin-6 (C-6), a lipophilic fluorescence dye, loaded NED was also prepared for cell uptake and tissue penetration studies.

Results : The developed liposome-microemulsion (LME) system, called Nano Eye Drop, showed particle size between 50-70 nm with entrapment efficiency above 95% in all pilot-scale batches (n=3). No significant change in size and entrapment efficiency was observed during a 6-month stability study at 25°C ± 2°C/60% RH ± 5% RH and 5°C ± 3°C. The product retained its sterility over the period of 4-weeks after opening the seal of the eye dropper. The C-6 loaded NED showed strong fluorescence (green) within 5 minutes of cell exposure (human corneal epithelial cells). The green fluorescence was also identified in the deep tissue of the corneal layer (rabbit eye). Cell viability above 75% was observed for all treatments (free DEXA, DEXA loaded NED, and blank NED). A sustained drug release from the nanoparticulate system was observed. In rabbits, the drug resided in the tear film for up to 12h after application with minimal plasma/aqueous humour concentration and no sign of corneal injury was observed.

Conclusions : This novel NED has significant potential as a treatment for ocular conditions with enhanced patient compliance likely due to the reduced dosing frequency required.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Graphical abstract