Sustained Subconjunctival Protein Delivery Using a Thermosetting Gel Delivery System

Abstract

Purpose: An effective treatment modality for posterior eye diseases would provide prolonged delivery of therapeutic agents, including macromolecules, to eye tissues using a safe and minimally invasive method. The goal of this study was to assess the ability of a thermosetting gel to deliver a fl uorescently labeled protein, Alexa 647 ovalbumin, to the choroid and retina of rats following a single subconjunctival injection of the gel. Additional experiments were performed to compare in vitro to in vivo ovalbumin release rates from the gel. Methods: The ovalbumin content of the eye tissues was monitored by spectrophotometric assays of tissue extracts of Alexa 647 ovalbumin from dissected sclera, choroid, and retina at time points ranging from 2 h to 14 days. At the same time points, fl uorescence microscopy images of tissue samples were also obtained. Measurement of intact ovalbumin was verifi ed by LDS-PAGE analysis of the tissue extract solutions. In vitro release of Alexa 488 ovalbumin into 37ºC PBS solutions from ovalbumin-loaded gel pellets was also monitored over time by spectrophotometric assay. In vivo ovalbumin release rates were determined by measurement of residual ovalbumin extracted from gel pellets removed from rat eyes at various time intervals. Results: Our results indicate that ovalbumin concentrations can be maintained at measurable levels in the sclera, choroid, and retina of rats for up to 14 days using the thermosetting gel delivery system. The concentration of ovalbumin exhibited a gradient that decreased from sclera to choroid and to retina. The in vitro release rate profi les were similar to the in vivo release profi les. Conclusions: Our fi ndings suggest that the thermosetting gel system may be a feasible method for safe and convenient sustained delivery of proteins to choroidal and retinal tissue in the posterior segments of the eye.

Subconjunctival injectable dendrimer-dexamethasone gel for the treatment of corneal inflammation

“…Subconjunctival injectable hydrogels can be a suitable option for sustained delivery and improving the bioavailability of steroids thereby avoiding frequent injections [38,39]. Additionally, targeting steroids to the inflammatory cell will be highly beneficial and may improve drug efficacy and reduce side effects.…”

Development of a Sustained-Release Voriconazole-Containing Thermogel for Subconjunctival Injection in Horses

“…13,[21][22][23] A number of barriers to ocular drug penetration, such as normal tear turnover, gravity-induced tear flow, blinking, induced lacrimation, and corneal and conjunctival epithelial tight junctions, limit the ability of topical medications to reach the anterior ocular segment. [24][25][26][27][28] Poor client/patient compliance can further reduce the volume and frequency of drug administration especially in horses due to their size, strong eyelid musculature, and lack of tolerance for repeated application of topical medications. Over the past decade, a variety of biocompatible, biodegradable polymers have been investigated for their potential as drug delivery carriers in an attempt to overcome the aforementioned barriers.…”

Ocular drug delivery systems: An overview

“…Rieke et al [99] have reported applicability of ReGel™ (biodegradable and thermosensitive triblock copolymer consisting of PLGA and PEG, in providing sustained release of a large molecule ovalbumin to the choroid and retina following subconjunctival administration in the rat eye. The ovalbumin concentrations were maintained at measurable levels in the sclera, choroid, and retina of rats over a period of 14 d. These results suggest feasibility of thermosetting gel system in providing sustained delivery of macromolecules to the posterior segment ocular tissues such as choroid and retina.…”