Improving drug delivery to the back of the eye by use of peptide‐eluting contact lenses
Authors: Toffoletto Nadia 
Published: December 2022

AbstractIntraocular injections are the current treatment of many pathologies affecting the posterior segment of the eye. However, this form of drug administration is invasive and may lead to serious side effects. Topical administration through eye drops, on the other hand, is associated with a low bioavailability and drug loss by lacrimation and systemic adsorption. Moreover, due to the required frequency of eye drops administration, a poor patient compliance is observed with the treatment. In the past decade, contact lenses have been suggested as non‐invasive drug reservoirs, which could deliver drugs in a sustained fashion, increase the drug residence time on the cornea and therefore its bioavailability. However, when targeting the posterior segment of the eye, drug released from contact lenses still encounter the barrier effect of the ocular tissues, which can significantly reduce the efficacy of delivery.Several strategies have been investigated to improve the permeation of drugs to the 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 demonstrated to cross the blood–brain barrier after systemic administration. In turn, Penetratin (a 16‐mer peptide) is a known cell penetrating peptide, which has been suggested as a carrier for drug delivery through many tissues, including the ocular membranes. Herein, the possibility of producing HEMA‐based contact lenses (CLs), simultaneously loaded with either KTPNH2 or Penetratin and an anti‐inflammatory drug (dexamethasone sodium phosphate, DexSod), was evaluated. Ex vivo permeability tests were conducted on excised porcine conjunctivas to assess the effect of the peptides on drug transport.Autodock software was used to predict the molecular interactions of the hydrogel monomers with the drug and peptides and identify the potential functional monomers. Besides HEMA, also acrylic acid (AAc) and aminopropyl methacrylamide (APMA) were added onto the CLs polymeric mixture as functional monomers with a high affinity for the peptides and DexSod, respectively. After polymerization, hydrogels were loaded by soaking in a dual solution of peptide and drug. In vitro release was performed in sink conditions. The light transmittance of the hydrogels was measured prior and after loading.Both peptides and drug were successfully loaded and released from the hydrogels. The presence of AAc and APMA increased the amount of peptides and DexSod loaded, respectively. APMA improved the drug release kinetic of DexSod, but its effect was hindered when both AAc and APMA were polymerized withing the hydrogel matrix. DexSod and the peptides were simultaneously released for at least 7 hours, which is compatible with the wearing time of daily contact lenses. The light transmittance of the hydrogels resulted higher than 90% at wavelengths above 500 nm, confirming their suitability as optical devices. Ex vivo tests revealed a significant increase (almost the double) in the permeability of DexSod in the presence of Penetratin.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.