Modulated release from implantable ocular silicone oil tamponade drug reservoirs

Abstract

Complicated cases of retinal detachment can be treated with silicone oil tamponades. There is the potential for silicone oil tamponades to have adjunctive drug releasing behaviour within the eye, however the lipophilic nature of silicone oil limits the number of drugs that are suitable, and drug release from the hydrophobic reservoir is uncontrolled. Here, a radiometric technique was developed to accurately measure drug solubility in silicone oil and measure release into culture media. All‐trans retinoic acid (atRA), a lipophilic drug known to act as an anti‐proliferative within the eye, was used throughout this work. Chain‐end modification of polydimethylsiloxane with atRA produced a polydimethylsiloxane retinoate (PDMS‐atRA), which was used as an additive to silicone oil to modify the solvent environment within the silicone oil and the distribution coefficient. Blends of PDMS‐atRA and silicone oil containing different concentrations of free atRA were produced. The presence of PDMS‐atRA in silicone oil had a positive effect on atRA solubility and the longevity of release in vitro. The drug release period was independent of atRA starting concentration and dependent on the PDMS‐atRA concentration in the blend. A clinically relevant release period of atRA over 7 weeks from a silicone oil blend with PDMS‐atRA was observed. © 2018 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 938–946

Biomaterials Targeting AMD: Are We There Yet?

“…A well-established delivery system is the silicone oil (SIO) tamponade which has been used clinically since 1958, usually for eye surgeries such as proliferative vitreoretinopathy (PVR) or retinal detachment/tears. Due to the close proximity to the retina, SIO can be dosed with drugs [61]. Despite its historical use, it is not without its drawbacks; a study showed 17.5% of neovascular AMD patients who underwent macular translocation surgery, followed by a SIO tamponade, went on to develop retinal detachment one month after removal [62] highlighting a need for an improved drug delivery system to the retina.…”

Amphiphilic additives in silicone oil tamponade and emulsification: an eye‐on‐a‐chip study

“…Recently, by chemically modifying the side branches of the polymer chains of SiO, solubility of lipophilic drugs, such as ibuprofen and all‐trans retinoic acid, are significantly enhanced (Cauldbeck et al. , ). This inspires the opportunity of using SiO as an effective reservoir to deliver and sustained release ophthalmic drugs into the eye.…”

“…The importance of this study is that previous studies on drug release in SiO did not take into account emulsification of SiO (Cauldbeck et al. , ). The pharmacokinetics of drugs is likely to be very different if SiO emulsifies as the total surface area of SiO changes (Lallemand et al.…”

“…Adding high-density materials yields SiO blends that possess a higher density than water to tackle inferior retinal diseases (Joussen et al 2007). Recently, by chemically modifying the side branches of the polymer chains of SiO, solubility of lipophilic drugs, such as ibuprofen and all-trans retinoic acid, are significantly enhanced (Cauldbeck et al 2016(Cauldbeck et al , 2018. This inspires the opportunity of using SiO as an effective reservoir to deliver and sustained release ophthalmic drugs into the eye.…”

“…To understand the role of amphiphilic additives in SiO on emulsification, we use a variety of SiO-soluble surfactants to test our hypothesis in this study. The importance of this study is that previous studies on drug release in SiO did not take into account emulsification of SiO (Cauldbeck et al 2016(Cauldbeck et al , 2018. The pharmacokinetics of drugs is likely to be very different if SiO emulsifies as the total surface area of SiO changes (Lallemand et al 2012).…”