Dexamethasone phosphate and penetratin co-eluting contact lenses: a strategy to enhance ocular drug permeability

Int J Pharm. 2024 Jan 25:650:123685. doi: 10.1016/j.ijpharm.2023.123685. Epub 2023 Dec 10.

Abstract

Contact lenses (CLs) have been suggested as drug delivery platforms capable of increasing the drug residence time on the cornea and therefore its bioavailability. However, when targeting the posterior segment of the eye, the drug released from CLs still encounters the barrier effect of the ocular tissues, which considerably reduces the efficacy of administration. This work aims at the development of CLs able to simultaneously deliver an anti-inflammatory drug (dexamethasone sodium phosphate) and a cell-penetrating peptide (penetratin), the latter acting as a drug carrier across the tissues. Hydroxyethyl methacrylate (HEMA)-based hydrogels were functionalized with acrylic acid (AAc) and/or aminopropyl methacrylamide (APMA) to serve as CL materials with increased affinity for the drug and peptide. APMA-functionalized hydrogels sustained the dual release for 8 h, which is compatible with the wearing time of daily CLs. Hydrogels demonstrated suitable light transmittance, swelling capacity and in vitro biocompatibility. The anti-inflammatory activity of the drug was not compromised by the presence of the peptide nor by sterilization. The ocular distribution of the drug after 6 h of CL wearing was evaluated in vivo in rabbits and revealed that the amount of drug in the cornea and aqueous humor significantly increased when the drug was co-delivered with penetratin.

Keywords: Anti-inflammatory; Dexamethasone; Drug-eluting contact lens; In vivo ocular biodistribution; Penetratin; Peptide.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents
  • Cell-Penetrating Peptides*
  • Contact Lenses*
  • Dexamethasone
  • Drug Carriers
  • Drug Delivery Systems
  • Hydrogels
  • Permeability
  • Rabbits

Substances

  • penetratin
  • Cell-Penetrating Peptides
  • dexamethasone 21-phosphate
  • Drug Carriers
  • Dexamethasone
  • Anti-Inflammatory Agents
  • Hydrogels