Dexamethasone distribution characteristic following controllable continuous sub-tenon drug delivery in rabbit

Drug delivery systems are required to be safe, minimally invasive and effectively delivery drug to the target tissues. But delivery drugs to the eye has not yet satisfied this need. Here, we focused on examining the distribution of dexamethasone (DEX) in ocular and plasmic samples following controllable continuous sub-Tenon drug delivery (CCSDD) of dexamethasone disodium phosphate (DEXP) in rabbit, and to compare that with two traditional routes: subconjunctival injection and intravenous injection. The DEX concentration was analyzed by Shimadzu LC-MS 2010 system. In CCSDD group, during observed 24 h, the mean DEX level in collected samples from highest to lowest following in order: sclera, cornea, retina/choroid, iris, plasma, aqueous humor, lens and vitreous body. In ocular solid tissue, the DEX level in posterior segment is higher than in anatomic corresponding anterior segment, but it is opposite in ocular fluid tissue. High levels of DEX were maintained at 12 h in the ocular tissue immediately after the administration. Even at 24 h, the mean DEX concentration was 31.72 ng/ml and 22.40 ng/ml in aqueous and vitreous, respectively. In CCSDD group, the ocular DEX exposure (AUC_0-24) is much higher and plasma exposure is much less than IV group, and it is also similar in SC group except iris. The amount of DEX levels are markedly increased in ocular tissues but it yield lower plasma levels indicating reduction of systemic absorption by CCSDD. Thus, CCSDD is an effective method of delivering DEX into anterior and posterior segment of the eye.