April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Enhanced Topical Delivery of a Novel Loteprednol Etabonate Ophthalmic Formulation
Author Affiliations & Notes
  • Lisa Schopf
    Preclinical Development, Kala Pharmaceuticals, Waltham, MA
  • Alexey Popov
    Preclinical Development, Kala Pharmaceuticals, Waltham, MA
  • Elizabeth M Enlow
    Preclinical Development, Kala Pharmaceuticals, Waltham, MA
  • James R Bourassa
    Preclinical Development, Kala Pharmaceuticals, Waltham, MA
  • Hongming R Chen
    Preclinical Development, Kala Pharmaceuticals, Waltham, MA
  • Footnotes
    Commercial Relationships Lisa Schopf, Kala Pharmaceuticals (E); Alexey Popov, Kala Pharmaceuticals (E); Elizabeth Enlow, Kala Pharmaceuticals (E); James Bourassa, Kala Pharmaceuticals (E); Hongming Chen, Kala Pharmaceuticals (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1533. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Lisa Schopf, Alexey Popov, Elizabeth M Enlow, James R Bourassa, Hongming R Chen; Enhanced Topical Delivery of a Novel Loteprednol Etabonate Ophthalmic Formulation. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1533.

      Download citation file:


      © 2017 Association for Research in Vision and Ophthalmology.

      ×
  • Supplements
Abstract

Purpose: To improve topical drug delivery to the eye, Kala has developed mucus penetrating particle (MPP) technology that facilitates drug penetration through pre-corneal mucus layer, providing superior delivery of drug to ocular tissues. The objective of this work was to evaluate a novel MPP formulation of loteprednol etabonate (LE-MPP).

Methods: Two in vivo distribution studies were conducted in rabbits to determine the ocular/systemic pharmacokinetic (PK) profiles of LE following topical administration of various LE-MPP concentrations. An additional distribution study was performed to compare LE-MPP 1.0% to commercially available Lotemax® (ophthalmic suspension) 0.5%. PK analysis was performed using WinNonlin software. To support the clinical evaluation of LE-MPP, a 28-day rabbit ocular toxicity study was conducted and standard ophthalmology, body weight, clinical signs, and histopathology of all ocular-related tissues and adrenal glands were evaluated.

Results: The dose-dependent concentration-time profiles of LE in aqueous humor (AH) revealed a proportional increase, as area under the curve, with doses from 0.4 to 1.0%, while the peak concentration plateaued at 0.6% with no further increase seen at 1.0%. The PK profiles of LE-MPP 1.0% drug product and Lotemax were compared in the AH, cornea, retina and plasma. The enhancement in LE exposure in all tissues was most pronounced over the first 3 hours after a single topical dose of LE-MPP as compared to Lotemax. The same tissues were examined after topical dosing of LE-MPP 1.0% or 0.25%. This analysis revealed that an increase in dose concentration increased exposure in the tissues assessed. The administration of LE-MPP 1.0% drug product to rabbits via ocular instillation four times daily for 28 days was well-tolerated and resulted in no test article-related observations except a mild decrease in body weight and body weight gain, a decrease in absolute lymphocyte count, adrenal cortical and hair follicle atrophy, effects that are expected for a corticosteroid and similar to those observed with Lotemax.

Conclusions: The PK results support the premise that the MPP technology can be used to enhance ocular exposure of topically applied therapeutic agents. The administration of LE-MPP 1.0% drug product was well-tolerated and the observed effects were considered secondary to the expected pharmacology of a corticosteroid and similar to those previously reported for Lotemax.

Keywords: 487 corticosteroids • 607 nanotechnology • 445 cataract  
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×