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Dale P. DeVore, Richard A. Eiferman, Bruce DeWoolfson; Sustained Delivery of Latanoprost from Collagen-based Depots. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3241.
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The purpose of this study was to measure in vitro release of Latanoprost from in situ polymerizing collagen gel formulations and collagen wafer depots. Subconjunctival implantation or injection of such depots could provide sustained delivery of Latanoprost for treatment of glaucoma.
Latanoprost (Xalatan) (13,14-dihydro-17-phenyl-18,19,20-trinor-prostaglandin F2a-1-isopropyl ester) was obtained from Sigma-Aldrich. Soluble, pepsin digested, bovine collagen for drug delivery formulations was purchased from Advanced Biomatrix. In situ polymerizing collagen was prepared by extensive dialysis of salt precipitated collagen against 0.035M EDTA with step-wise increase in pH to 7.5. Collagen wafers were prepared by UV irradiation of chemically modified collagen in 1cm diameter molds. Latanoprost was dissolved in ethanol and added to polymerizing collagen gels and chemically modified gels to provide gel depots containing 250µg/100µLand wafer depots containing 200µg/wafer. Wafer depots were formed by UV irradiation in nitrogen for 15-18 minutes. Gels and wafers were incubated in 1.0 mL of physiological saline at 37ºC. The entire 1.0mL volume was removed at time periods ranging from 1 day to 27 days and replaced with 1.0mL of fresh buffer. Latanoprost concentration in buffer aliquots was measured by HPLC analysis (Millennium Research Laboratories).
HPLC analysis showed a large initial release of Latanoprost from polymerizing gels added directly to buffer solution followed by sustained release averaging 1.4µg/day. Polymerizing gels partially pre-polymerized before placing in buffer solution showed a reduced initial release followed by sustained release averaging 1.68µg/day. Release from UV polymerized wafers showed a uniform release for more than 30 days without an initial burst. In situ polymerizing collagen gels and solid collagen wafers produced sustained in vitro release of Latanoprost for more than 30 days. It is proposed that such collagen depots could be injected or implanted in conjunctival tissue to provide sustained release of Latanoprost for treatment of glaucoma.
In situ polymerizing collagen gels and solid collagen wafers produced sustained in vitro release of Latanoprost for more than 30 days. It is proposed that such collagen depots could be injected or implanted in the subconjunctival space to provide sustained release of Latanoprost for treatment of glaucoma.
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