Abstract
Purpose: :
To evaluate the ocular tissue distribution of fluorescent drug mimics from our non-biodegradable polymeric capsule device placed episclerally in rats.
Methods: :
A polydimethylsiloxane master mold for the capsule was first fabricated via a microfabrication technique that used an AutoCAD design and a micro-processing machine. A mixture of polyethylene glycol dimethacrylate (PEGDM) and collagen microparticles (COL), and triethylene glycol dimethacrylate (TEGDM) were individually UV cured in the molds to obtain a controlled release membrane and a drug reservoir. After loading drug mimics, the membrane was sealed to the reservoir by UV curing. To estimate the amounts of fluorescent drugs that had diffused out of the capsules, the fluorescent intensities of phosphate-buffered solution (PBS) were measured spectrofluorometrically. The capsules were placed onto the sclera of rat eyes. Fluorescent images were captured using a handheld retinal camera for fluorescein angiography to document the fluorescence distributions around the capsules and the sclerae. Histological examinations and fluorescent measurements of ocular tissues were performed to evaluate the ocular tissue distribution of drug mimics.
Results: :
Fluorescence intensity reached detectable levels in the retina, choroid/retinal pigment epithelium, and vitreous body 15 days after episcleral implantation of the device. In vitro release profiles in PBS were similar to in vivo fluorescent distributions. Histological examinations showed that the fluorescent drug mimics had migrated to the retinal pigment epithelium, retina, and vitreous, which indicated that transscleral delivery had been achieved.
Conclusions: :
Transscleral drug delivery using a non-biodegradable capsule device was demonstrated. The device may offer a less-invasive method of delivery to achieve sustained release of medications for intravitreal drug delivery and the treatment of various retinal diseases.
Keywords: retina • sclera • neuroprotection