Hollow Microcapsules as Periocular Drug Depot for Sustained Release of Anti-VEGF Protein

Abstract

Diseases affecting the posterior segment of the eye such as age-related macular degeneration and diabetic retinopathy are leading causes of blindness all over the world. The current treatment regimen for such diseases involves repeated intravitreal injections of anti- Vascular Endothelial Growth Factor (VEGF) proteins. This method is highly invasive and can lead to severe complications. In an attempt to develop less invasive alternatives, we propose the use of a controlled release system consisting of anti-VEGF loaded hollow microcapsules that can be administered periocularly to form drug eluting depots on the episcleral surface. The microcapsules with either positive or negative surface charge were prepared by a layer by layer approach and showed pH responsive permeability switching. An ex vivo experiment using porcine sclera indicated positively charged microcapsules remained on the episcleral surface over four days while the negatively charged microcapsules were washed away. These positively charged microcapsules were then loaded with anti-VEGF protein ranibizumab using pH dependent permeability switching and protein release from the microcapsules were studied using an in vitro setup. An ex vivo experiment utilizing porcine sclera demonstrated sustained release of ranibizumab over seven days with zero-order kinetics.

Multimodal Imaging of the Bimatoprost Sustained Release Implant (Durysta) after Intracameral and Middle Segment Delivery

“…Taken together this reduces side-effects, maximizes efficacy while also increasing patient compliance. [17][18][19] In regards to glaucoma specifically, all glaucoma drops have ocular surface toxicity but none are designed to act on the ocular surface. Moreover, many have come to hypothesize that IOP fluctuation may be more damaging than absolute IOP; therefore a means of maintaining nearly constant intraocular drug concentration and as corollary more controlled pressure, could be a game changer for glaucoma patients.…”

Preparation and Application of a Natural Microspheric Soil Conditioner Based on Gelatin, Sodium Alginate, and Zeolite

“…Deionized water (100 mL) was added to measure the concentration of urea for the sustained release experiment. The concentration of urea in the sustained release solution was obtained through the absorbance measured by UV–vis, and the sustained release ratio was calculated . The cumulative release rate (CRR) of urea was calculated according to the following formula: CRR ( % ) = C t × V normalT + prefix∑ 0 t − 1 C t × V t M 0 × 100 where C t and V t are the concentration and volume of the solution at t .…”

“…The concentration of urea in the sustained release solution was obtained through the absorbance measured by UV−vis, and the sustained release ratio was calculated. 27 The cumulative release rate (CRR) of urea was calculated according to the following formula:…”

Overcoming Treatment Challenges in Posterior Segment Diseases with Biodegradable Nano-Based Drug Delivery Systems

“…Anecortave cortisone administered through juxtascleral injection provided a sustained release up to 6 months for age-related macular degeneration treatment [19]. The juxtascleral injection of hollow microcapsules loaded with an anti-vascular endothelial growth factor protein for macular degeneration and diabetic retinopathy treatment can form a depot on the episcleral surface [20]. Additionally, transscleral microneedles have been designed for retinal gene therapy [21].…”