PURPOSE: The aim of this study was to investigate the extent if recombinant human hyaluronidase (rhuPH20) can enhance trans-scleral penetration of sub-Tenon's dexamethasone (DM) into the posterior segment of the eye. METHODS: rhuPH20 was purified from conditioned media through a series of ion exchange, hydrophobic interaction, aminophenylboronate, and hydroxyapatite chromatography to greater than 90% purity based upon specific activity. Only the right eye of each rabbit was injected. The first group (n = 16) received an injection of DM and rhuPH20, whereas the second group (n = 16) received DM only. The eyes were enucleated 1, 2, 3, and 6 h after the injection, and the choroid, retina, vitreous, aqueous, and serum were harvested. DM concentration was assessed by mass spectrometry. Histology (n = 2) and immunohistochemistry (n = 2) was performed to detect toxicity and the presence of the rHuPH20, respectively. RESULTS: We observed no histopathologic damage to ocular tissues after sub-Tenon's injection. This enzyme significantly increased DM level in the choroid and the retina 3 h after administration. The rise in levels was transient returning to normal levels by 6 h. CONCLUSIONS: Sub-Tenon's coinjection of rHuPH20 with DM resulted in a general increase in DM levels in ocular tissues and the serum, with significant increase in the choroid and the retina, 3 h after administration.
PURPOSE: The aim of this study was to investigate the extent if recombinant human hyaluronidase (rhuPH20) can enhance trans-scleral penetration of sub-Tenon's dexamethasone (DM) into the posterior segment of the eye. METHODS: rhuPH20 was purified from conditioned media through a series of ion exchange, hydrophobic interaction, aminophenylboronate, and hydroxyapatite chromatography to greater than 90% purity based upon specific activity. Only the right eye of each rabbit was injected. The first group (n = 16) received an injection of DM and rhuPH20, whereas the second group (n = 16) received DM only. The eyes were enucleated 1, 2, 3, and 6 h after the injection, and the choroid, retina, vitreous, aqueous, and serum were harvested. DM concentration was assessed by mass spectrometry. Histology (n = 2) and immunohistochemistry (n = 2) was performed to detect toxicity and the presence of the rHuPH20, respectively. RESULTS: We observed no histopathologic damage to ocular tissues after sub-Tenon's injection. This enzyme significantly increased DM level in the choroid and the retina 3 h after administration. The rise in levels was transient returning to normal levels by 6 h. CONCLUSIONS: Sub-Tenon's coinjection of rHuPH20 with DM resulted in a general increase in DM levels in ocular tissues and the serum, with significant increase in the choroid and the retina, 3 h after administration.
Authors: David J Miller; S Kevin Li; Anthony L Tuitupou; Rajan P Kochambilli; Kongnara Papangkorn; Donald C Mix; William I Higuchi; John W Higuchi Journal: J Ocul Pharmacol Ther Date: 2008-08 Impact factor: 2.671