Ex vivo models to evaluate the role of ocular melanin in trans-scleral drug delivery

Silvia Pescina, Patrizia Santi, Giulio Ferrari, Cristina Padula, Pierugo Cavallini, Paolo Govoni, Sara Nicoli

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Trans-scleral delivery is nowadays considered as a possible way to deliver drugs to the posterior segment of the eye. Despite the potentiality of this administration route, there is a lack of fundamental knowledge on the role of the numerous barriers involved. The aim of this work was to develop an easy and cheap ex vivo method to evaluate the barrier properties of the choroid-Bruch's layer and in particular to estimate the role of melanin in drug diffusion through ocular tissues. In vitro binding studies were performed to estimate drug affinity for melanin; model molecules used were methylene blue, propranolol, levofloxacin and methylprednisolone sodium succinate. The ex vivo model set up is based on porcine eye bulbs with light blue iris or brown iris. While the choroid of brown eyes is dark, the choroid of blue eyes is transparent, due to the absence of melanin. Permeation experiments using pigmented and not-pigmented porcine tissues gave the opportunity to discriminate between the barrier role of choroid-Bruch's membrane as such and the barrier role of melanin. Ex vivo permeation experiments can be performed using isolated choroid-Bruch's or the sclera-choroid-Bruch's layer. In this last case, it is possible to take into account also the barrier role of the sclera that tends to decrease the drug concentration at the sclera/choroid interface, thus amplifying the effect of melanin. The data obtained in this paper indicate that for some drugs melanin can really represent a barrier and the effect can imply a lower drug flux or simply a longer lag time depending on the kind of drug and the concentration applied. However, it is a saturable barrier, thus its effect can probably be overtaken by high doses or multiple administrations. The ex vivo model set up can help to refine computational models, to better evaluate the interplay among static, dynamic and metabolic barriers. Additionally, since human eyes display a full range of pigmentation, the model could also be useful to investigate the possible influence of pigmentation phenotype on trans-scleral delivery.

Original languageEnglish
Pages (from-to)475-483
Number of pages9
JournalEuropean Journal of Pharmaceutical Sciences
Volume46
Issue number5
DOIs
Publication statusPublished - Aug 15 2012

Fingerprint

Choroid
Melanins
Sclera
Pharmaceutical Preparations
Pigmentation
Iris
Swine
Posterior Eye Segment
Methylprednisolone Hemisuccinate
Bruch Membrane
Levofloxacin
Methylene Blue
Propranolol
Phenotype

Keywords

  • Choroid-Bruch's membrane
  • Ex vivo model
  • Melanin
  • Ocular delivery
  • Trans-scleral

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Ex vivo models to evaluate the role of ocular melanin in trans-scleral drug delivery. / Pescina, Silvia; Santi, Patrizia; Ferrari, Giulio; Padula, Cristina; Cavallini, Pierugo; Govoni, Paolo; Nicoli, Sara.

In: European Journal of Pharmaceutical Sciences, Vol. 46, No. 5, 15.08.2012, p. 475-483.

Research output: Contribution to journalArticle

Pescina, Silvia ; Santi, Patrizia ; Ferrari, Giulio ; Padula, Cristina ; Cavallini, Pierugo ; Govoni, Paolo ; Nicoli, Sara. / Ex vivo models to evaluate the role of ocular melanin in trans-scleral drug delivery. In: European Journal of Pharmaceutical Sciences. 2012 ; Vol. 46, No. 5. pp. 475-483.
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