文献类型：期刊文献

英文题名：Intravitreal controlled release of dexamethasone from engineered microparticles of porous silicon dioxide

作者：Wang, Chengyun[1,2,3,4];Hou, Huiyuan[1];Nan, Kaihui[1];Sailor, Michael J.[2];Freeman, William R.[1];Cheng, Lingyun[1]

机构：[1]Univ Calif San Diego, Shiley Eye Ctr, Jacobs Retina Ctr, Dept Ophthalmol, La Jolla, CA 92037 USA;[2]Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA;[3]E China Univ Sci & Technol, Key Lab Adv Mat, Shanghai 200237, Peoples R China;[4]E China Univ Sci & Technol, Inst Fine Chem, Shanghai 200237, Peoples R China

年份：2014

卷号：129

起止页码：74

外文期刊名：EXPERIMENTAL EYE RESEARCH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000346893800011)】；

基金：Financial support: This study was supported by the National Institutes of Health under grant number NIH EY020617; P30EY022589.The work was also partially supported by the grant from Research to Prevent Blindness to UCSD.

语种：英文

外文关键词：Intravitreal drug delivery; Porous silicon particle; Dexamethasone; Sustained release; Rabbit eye

摘要：Dexamethasone is a glucocorticoid that is widely used in the ophthalmic arena. The recent FDA approved dexamethasone implant can provide a three month efficacy but with high rate of drug related cataract and high intraocular pressure (IOP). It seems that higher steroid in aqueous humor and around lens may be associated with these complications based on clinical fact that higher IOP was observed with intravitreal triamcinolone acetonide (TA) than with subtenon TA. We hypothesize that placing a sustained dexamethasone release system near back of the eye through a fine needle can maximize efficacy while mitigate higher rate of IOP rise and cataract. To develop a sustained intravitreal dexamethasone delivery system, porous silicon dioxide (pSiO(2)) microparticles were fabricated and functionalized with amines as well as carboxyl groups. Dexamethasone was conjugated to pSiO(2) through the Steglich Esterification Reaction between hydroxyl of dexamethasone and carboxyl groups on the pSiO(2). The drug loading was confirmed by Fourier transform infrared spectroscopy (FTIR) and loading efficiency was quantitated using thermogravimetric analysis (TGA). In vitro release was conducted for three months and dexamethasone was confirmed in the released samples using liquid chromatography-tandem mass spectrometry (LC/MS/MS). A pilot ocular safety and determination of vitreous drug level was performed in rabbit eyes. The drug loading study demonstrated that loading efficiency was from 5.96% to 10.77% depending on the loading reaction time, being higher with longer loading reaction time before reaching saturation around 7 days. In vitro drug release study revealed that dexamethasone release from pSiO(2) particles was sustainable for over 90 days and was 80 days longer than free dexamethasone or infiltration-loaded pSiO(2) particle formulation in the same setting. Pilot in vivo study demonstrated no sign of ocular adverse reaction in rabbit eyes following a single 3 mg intravitreal injection and free drug level at 2-week was 107.23 +/- 10.54 ng/mL that is well above the therapeutic level but only around 20% level of dexamethasone released from OZURDEX (R) (dexamethasone intravitreal implant) in a rabbit eye model. In conclusion, dexamethasone is able to covalently load to the pSiO(2) particles and provide sustained drug release for at least 3 months in vitro. Intravitreal injection of these particles were well tolerated in rabbit eyes and free drug level in vitreous at 2-week was well above the therapeutic level. (C) 2014 Elsevier Ltd. All rights reserved.