Peptide-eluting contact lenses for an improved delivery of dexamethasone to the back of the eye

Abstract

Purpose : To avoid the need of intraocular injections, several strategies have been investigated to improve the permeation of topical drug delivery to posterior segment of the eye, such as the use of peptides as drug carriers. Kyotorphin (L-Tyr-L-Arg) is a small endogenous neuropeptide, whose derivatives (e.g. KTPNH₂) were previously designed to increase membrane permeability. Penetratin (a 16-mer peptide) is a known cell penetrating peptide, which have been suggested as a carrier for drug delivery through many tissues, including the ocular membranes. Herein, the possibility of producing therapeutic contact lenses (CLs), loaded with either KTPNH₂, Penetratin or a dexamethasone-KTPNH₂ complex (Dex-KTPNH₂), was evaluated with the aim of increasing the delivery efficiency of dexamethasone to the back of the eye.

Methods : Hydrogels of HEMA-TRIS-NVP were investigated as potential CL backbone. Autodock software was used to model the molecular interactions between the monomers and the peptide and identify potential functional monomers. After polymerization, hydrogel discs (N ≥ 3) were loaded by soaking in a peptide solution (1mg/mL). The effect of pre-soaking in a solution of vitamin E in ethanol was investigated to prolong the release time. Drug-release was performed in vitro in sink conditions. The swelling behavior and light transmittance of the hydrogels were tested prior and after loading.

Results : Molecular simulation suggested a strong interaction between acrylic acid (AAc) and the peptides. Therefore, AAc was incorporated in the prepolymer mixture as a functional monomer. The light transmittance of the hydrogels resulted higher than 90% at wavelengths above 500 nm. The peptide uptake and the swelling increased with the addition of AAc for all the tested molecules, while the presence of vitamin E was associated to a lower swelling. The pre-soaking in vitamin E and the presence of the functional monomer prolonged the release time of KTPNH₂ up to 8h. Unmodified HEMA-TRIS-NVP hydrogels were able to sustain the release of Penetratin or the Dex-KTPNH₂ complex for more than 24 hours (Figure 1).

Conclusions : The obtained results shall contribute for the development of new topical treatment forms, able to provide a therapeutic effect in the back of the eye without need of intraocular injections.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

In vitro release of KTPNH₂, Penetratin and Dex-KTPNH₂ from HEMA-TRIS-NVP hydrogels.