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An Ilomastat-CD Eye Drop Formulation to Treat Ocular Scarring
Abeer H A Mohamed-Ahmed1, Alastair Lockwood1, He Li2
1UCL School of Pharmacy, London, United Kingdom 2UCL Institute of Ophthalmology, London, United Kingdom.
Purpose:
The purpose of this study was to develop a topical matrix metalloproteinase inhibitor preparation for antiscarring therapy.
Methods:
The broad spectrum matrix metalloproteinase inhibitor ilomastat was formulated using 2-hydroxypropyl-β-cyclodextrin in aqueous solution. In vitro activity of ilomastat-cyclodextrin (ilomastat-CD) was examined using fibroblasts seeded in collagen. Permeation of ilomastat-CD eye drop through pig eye conjunctiva was confirmed using Franz diffusion cells. Ilomastat-CD eye drop was applied to rabbit eyes in vivo, and the distribution of ilomastat in ocular tissues and fluids was determined by liquid chromatography-mass spectroscopy.
Results:
The aqueous solubility of ilomastat-CD was ∼1000 microg/mL in water and 1400 microg/mL in PBS (pH 7.4), which is greater than ilomastat alone (140 and 160 microg/mL in water and PBS, respectively). The in vitro activity of ilomastat-CD to inhibit collagen contraction in the presence of human Tenon fibroblast cells was unchanged compared to uncomplexed ilomastat. Topically administered ilomastat-CD in vivo to rabbit eyes resulted in a therapeutic concentration of ilomastat being present in the sclera and conjunctiva and within the aqueous humor.
Conclusions:
Ilomastat-CD has the potential to be formulated as an eye drop for use as an antifibrotic, which may have implications for the prevention of scarring in many settings, for example glaucoma filtration surgery.
