Solid implantable devices for sustained drug delivery.

Abstract Currently, the treatment for ocular neovascular diseases, including diabetic macular edema (DME) and age-related macular degeneration (AMD), mainly involves repeated intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs. Although it can preserve vision, repeated injections are an invasive treatment modality, leading to serious complications and reducing patient adherence to treatment. To reduce the frequency of administration, prolong the time of drug action, and avoid repeated intravitreal injections, the combination of sustained-release materials with anti-VEGF drug therapy has become an emphasis in ophthalmology. In this review, we highlight the current state of anti-VEGF technology, its challenges, and the sustained-release strategies under investigation or being used in clinical practice. Both continuous release and considerable therapeutic effects can be achieved by encapsulating anti-VEGF drugs in sustained-release materials to minimize the number of intravitreal injections. At present, two sustained-release materials are being tested in clinical research, and although basic research shows the strong therapeutic application prospects of extended-release drugs, its challenges mainly involve the discrepancy between the release rates in vitro and the efficiency of the drugs in vivo. Briefly, sustained release of anti-VEGF agents is an advantageous strategy for treating retinal angiogenesis.

https://www.dovepress.com/getfile.php?fileID=84122

Progress and Challenges of Anti-VEGF Agents and Their Sustained-Release Strategies for Retinal Angiogenesis

Recent advances and future prospects: current status and challenges of the intraocular injection of drugs for vitreoretinal diseases.

Implantable sustained-release drug delivery systems: a revolution for ocular therapeutics

The administration of anti-vascular endothelial growth factor drugs in the posterior eye segment with sustained release through less invasive methods is a challenge in the treatment of age-related macular disease. We developed a flexible capsule device using porous poly(dimethylsiloxane) (PDMS) that was able to release ranibizumab. The porous PDMS sheet was fabricated by salt-leaching of a micro-sectioned PDMS sheet containing salt microparticles. Observation with scanning electron microscopy revealed that the pore densities could be adjusted by the concentration of salt. The in vitro release study showed that the release rate of fluorescein isothiocyanate-tagged albumin could be adjusted based on the pore density of the porous PDMS sheet. Ranibizumab could be released in a sustained-release manner for 16 weeks. The device was implanted on the sclera; its efficacy in terms of the suppression of laser-induced choroidal neovascularization (CNV) in rats was compared with that of monthly intravitreal injections of ranibizumab. At 8 and 18 weeks after implantation, the CNV area was significantly reduced in rats that received the ranibizumab-releasing device compared with those that received the placebo device. However, although monthly intravitreal injections of ranibizumab reduced CNV for 8 weeks, this reduction was not sustained for 18 weeks. In conclusion, we demonstrated a novel controlled-release device using a porous PDMS sheet that could suppress CNV via a less invasive transscleral route versus intravitreal injections. This device may also reduce the occurrence of side effects associated with frequent intravitreal injections. 

/pdf/release-of-ranibizumab-using-a-porous-poly-dimethylsiloxane-ccm4mcoq.pdf

Release of ranibizumab using a porous poly(dimethylsiloxane) capsule suppressed laser-induced choroidal neovascularization via the transscleral route

Transscleral sustained ranibizumab delivery using an episcleral implantable device: Suppression of laser-induced choroidal neovascularization in rats.

In this study, we developed a subcutaneous insulin-releasing device consisting of a disk-shaped capsule and drug formulation comprised of poly(ethylene glycol) dimethacrylates, then evaluated its efficacy on retinal function in streptozotocin (STZ)-induced diabetic rats. In vitro release studies showed that recombinant human insulin was released with a constant rate for more than 30 days. The device was able to maintain a basal level of blood glucose in diabetic rats for a prolonged period of more than 30 days, simultaneously preventing a decrease in body weight. For assessing the pharmacological effect of the device on retinal function in diabetic rats, electroretinograms were conducted for 12 weeks. The reduction in amplitude and delay in implicit time were attenuated by the device during the initial 4 weeks of application. The increase in gene expression of protein kinase C (PKC)-γ and caspase-3 in the diabetic retina was also attenuated by the device. Immunohistochemistry showed that the increase in glial fibrillary acidic protein expression in the diabetic retina was attenuated by the device. Histological evaluation of subcutaneous tissue around the device showed the biocompatibility of the device. In conclusion, the insulin-releasing device attenuated the reduction of retinal function in STZ-induced diabetic conditions for 4 weeks and the efficacy of the device might be partially related to PKC signaling in the retina. The long-term ability to control the blood glucose level might help to reduce the daily frequency of insulin injections.

Effect of sustained insulin-releasing device made of poly(ethylene glycol) dimethacrylates on retinal function in streptozotocin-induced diabetic rats

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Transscleral sustained ranibizumab delivery using an episcleral implantable device: Suppression of laser-induced choroidal neovascularization in rats.

Effect of sustained insulin-releasing device made of poly(ethylene glycol) dimethacrylates on retinal function in streptozotocin-induced diabetic rats