A sustained dual drug delivery system for proliferative vitreoretinopathy

Abstract

Proliferative vitreoretinopathy (PVR) is a significant threat for vision recovery from retinal detachment or ocular trauma. Currently, no approved pharmacological intervention to prevent PVR. Daunorubicin (DNR) and dexamethasone (DEX) were sequentially loaded into oxidized porous silicon (pSiO 2) particles by covalent conjugation. The DNR þ DEX-loaded particles, and control particles loaded with DNR only and DEX only were incubated with RPE-populated collagen for daily gel surface quantitation. Toxicity was monitored by ophthalmic examinations and histological evaluation 21 days after injection. At 3rd week following intravitreal injection, a localized retinal detachment (RD) was created by subretinal injection of Healon in all pretreated eyes in addition to 3 non-interventional control eyes. 10 mg of bromodeoxyuridine (BrdU) was injected into the vitreous 4 h before sacrifice on day 3 after RD induction. Retinal sections were stained for glial fibrillary green protein (GFAP) and BrdU to identify activated glial cells and retinal cell proliferation. The studies demonstrated that all three pSiO 2 particle types were well tolerated in vivo. DNR alone and DNR þ DEX combination formulations demonstrated equally strong suppression on gel contraction (least square mean area of the gel: control ¼ 1.71 vs. 30DNR ¼ 1.85 or 30/40Dual ¼ 1.83, p < .05). Eyes pretreated with pSiO 2 ÀDNR þ DEX exhibited the least GFAP activation (least square mean intensity mm À2 : Dual ¼ 4.03, DNR ¼ 7.76, Dex ¼ 16.23, control ¼ 29.11, p < .05) and BrdU expression (Mean number of BrdU positive cells per mm of retina: Dual ¼ 2.77, DNR ¼ 4.58, Dex ¼ 4.01, control ¼ 6.16, p < .05). The synergistic effect of a sustained release pSiO 2 ÀDNR/DEX showed promise for the prevention of PVR development while reducing the necessary therapeutic concentration of each drug.

Intravitreal slow-release dexamethasone alleviates traumatic proliferative vitreoretinopathy by inhibiting persistent inflammation and Müller cell gliosis in rabbits

“…Müller cell gliosis also plays an important role in the development of PVR [15,[44][45] . Xiao et al [13] reported that Müller cells were activated on day 3 after retinal detachment induced by infusing sodium hyaluronate into the subretinal space through a tiny retinotomy. However, in the case of traumatic PVR, the status and extent of Müller cell reaction have not yet been fully elucidated.…”

“…Therefore, it is needed for further research on the progression of traumatic PVR. Following ocular trauma, gliotic changes in the retina have an essential role in PVR pathologic process associated with retinal stiffness and shortening [10][11][12][13] ; and the primary participating cellular components are Müller glial cells [14][15] . Glial fibrillary acid protein (GFAP) is considered a sensitive biomarker for reactive Müller gliosis and correlates positively with PVR severity [16] .…”

Therapeutic Applications of the CRISPR-Cas System

“…The main focus of clinical application is the creation of nanocarriers to deliver CRISPR-Cas9 into specific cancer cells [ 90 ]. Polymer nanoparticles [ 88 , 91 , 92 ], lipid nanoparticles [ 93 , 94 , 95 ], and porous nanoparticle [ 96 ] are used as nanocarriers.…”

Ligand-independent Activation of Platelet-derived Growth Factor Receptor β promotes contraction of retinal pigment epithelial cells

“…The tracking force of the ERMs causes retinal detachment [8]. At present there is no approved medicine for this eye disease [9]; the only treatment option with the surgery leads to the poor sight recovery [10,11]. Therefore, it is urgent to develop a pharmacological approach for the therapy of PVR.…”