Evaluation of RGD peptide hydrogel in the posterior segment of the rabbit eye

Abstract

The aim of this study was to evaluate the biocompatibility and biodegradability of RGD peptide hydrogel in the posterior segment of the eye as a biomaterial potentially useful for sustained drug delivery systems. RGD peptide hydrogel was injected into the vitreous cavity and suprachoroidal space of rabbit eyes. Clinical follow-up and histological observation were performed up to four weeks. The biodegradability was also evaluated by the lifetime of the hydrogel which was defined by ophthalmoscopic observation or ultrasonography. The results showed that RGD peptide hydrogel was well tolerated in the vitreous cavity and suprachoroidal space, and disappeared from the injection sites progressively. As for suprachoroidal injection, the hydrogel was clearly identified by ultrasound echography and was confirmed innoxious to the retinal vessels by fluorescein angiography. Histological observations showed that the structures of retina, choroid and other tissues around the injection site remained normal after the injection. The lifetime of the hydrogel was 25.7 ± 2.65 days and 14.3 ± 3.3 days in the vitreous cavity and suprachoroidal space, respectively. The results obtained demonstrated that RGD peptide hydrogel, which showed excellent biocompatibility and favorable biodegradability in the posterior segment of rabbit eyes, appears to be a promising biomaterial to deliver drugs focally to the choroid and the retina.

Thickness and Closure Kinetics of the Suprachoroidal Space Following Microneedle Injection of Liquid Formulations

“…Other formulations, 1 , 7 , 15 , 21 , 24 , 31 – 36 including in situ gelling formulations (such as poly[ortho esters] 7 or polycaprolactone dimethacrylate 15 ), have been injected into the SCS, but those studies did not report on SCS thickness or closure times. These formulations may exhibit behavior, at least initially, that is qualitatively similar to that seen with CMC or Discovisc in this study, depending in part on formulation viscosity.…”

Drug Delivery via the Suprachoroidal Space for the Treatment of Retinal Diseases

“…Different biopolymers were studied to target this issue and were found to be biocompatible and efficient, extending the lifetime of the material injected. Such biopolymers include peptide hydrogel [ 66 ], which was injected into the SCS of rabbits in vivo with a lifetime of 14.3 ± 3.3 days; poly ortho ester (POE) [ 67 ], injected into the SCS of rabbits in vivo, that was detectable for about 6 months; light-activated polycaprolactone dimethacrylate (PCM) and hydroxyethyl methacrylate (HEMA)-based gel network, entrapping bevacizumab injected into the SCS of rabbit eyes ex vivo and rat eyes in vivo, which released bevacizumab for 4 months and maintained the stability of VEGF-binding activity [ 38 ]; a surgically implanted sustained-release cyclosporine device that was effective in controlling uveitis in horses [ 68 , 69 ]; a sustained release formulation of dexamethasone injected to the SCS was investigated with lapotine [ 70 ] and polyurethane [ 71 ] biopolymer implants with reported half-life of 36.4 days with lapotine and dexamethasone levels for up to 42 days with polyurethane implant; and acriflavine, an inhibitor of the angiogenic factor HIF-1, incorporated to poly lactic-co-glycolic acid injected into the SCS of rats, which was found to suppress choroidal neovascularization for at least 18 weeks [ 72 ].…”

The suprachoroidal space as a route of administration to the posterior segment of the eye

“…One common strategy is to encapsulate the drug within polymeric microparticles or implants. Monolithic implants have been surgically placed[46, 47] or injected in situ [34, 39, 43, 62] within the SCS. They can result in controlled release over months to the SCS and adjacent tissues surrounding the implant.…”

“…Various biopolymers that can be used to control drug release have been tested within the SCS with good biocompatibility[34, 39, 43, 46, 62, 66]. A significant foreign body reaction to the polylactic acid microparticles was reported, but it was unclear if this was a sterility or biocompatibility issue[72].…”