Laser irradiation of ocular tissues to enhance drug delivery

Int J Pharm. 2021 Mar 1:596:120282. doi: 10.1016/j.ijpharm.2021.120282. Epub 2021 Jan 26.

Abstract

Scleral and corneal membranes represent substantial barriers against drug delivery to the eye. Conventional hypodermic needles-based intraocular injections are clinically employed to overcome these barriers. This study, for the first time, investigated a non-invasive alternative to intraocular injections by laser irradiation of ocular tissues. The P.L.E.A.S.E.® laser device was applied on excised porcine scleral and corneal tissues, which showed linear relationships between depths of laser-created micropores and laser fluences at range 8.9-444.4 J/cm2. Deeper and wider micropores were observed in scleral relative to corneal tissues. The permeation of rhodamine B and fluorescein isothiocyanate (FITC)-dextran were investigated through ocular tissues at different laser parameters (laser fluences 0-44.4 J/cm2 and micropore densities 7.5 and 15%). Both molecules showed enhanced permeation through ocular tissues on laser irradiation. Maximum transscleral permeation of the molecules was attained at laser fluence 8.9 J/cm2 and micropore density 15%. Transcorneal permeation of rhodamine B increased with increasing either laser fluence or micropore density, while that of FITC-dextran was not affected by either parameter. The transscleral water loss increased significantly after laser irradiation then returned to the baseline values within 24 h, indicating healing of the laser-created micropores. Laser irradiation is a promising technique to enhance intraocular delivery of both small and large molecule drugs.

Keywords: Corneal permeability; Laser microporation; Micropores; Ocular delivery; Optical coherence tomography; Scleral permeability.

MeSH terms

  • Animals
  • Drug Delivery Systems*
  • Lasers
  • Needles
  • Pharmaceutical Preparations*
  • Sclera
  • Swine

Substances

  • Pharmaceutical Preparations