Department of Chemistry, University of Liverpool, Crown Street, L69 7ZD, UK.
Department of Chemistry, University of Liverpool, Crown Street, L69 7ZD, UK; Department of Eye and Vision Science, University of Liverpool, Liverpool, UK.
J Control Release. 2016 Dec 28;244(Pt A):41-51. doi: 10.1016/j.jconrel.2016.11.010. Epub 2016 Nov 12.
In a number of cases of retinal detachment, treatment may require the removal of the vitreous humour within the eye and replacement with silicone oil to aid healing of the retina. The insertion of silicone oil offers the opportunity to also deliver drugs to the inside of the eye; however, drug solubility in silicone oil is poor and release from this hydrophobic drug reservoir is not readily controlled. Here, we have designed a range of statistical graft copolymers that incorporate dimethylsiloxane and ethylene glycol repeat units within the side chains, allowing short chains of oligo(ethylene glycol) to be solubilised within silicone oil and provide hydrogen bond acceptor sites to interact with acid functional drug molecules. Our hypothesis included the potential for such interactions to be able to delay/control drug release and for polymer architecture and composition to play a role in the silicone oil miscibility of the targeted polymers. This strategy has been successfully demonstrated using both ibuprofen and all-trans retinoic acid; drugs with anti-inflammatory and anti-proliferation activity. After the copolymers were shown to be non-toxic to retinal pigment epithelial cells, studies of drug release using radiochemical approaches showed that the presence of 10v/v% of a linear graft copolymer could extend ibuprofen release over three-fold (from 3days to >9days) whilst the release of all-trans retinoic from the silicone oil phase was extended to >72days. These timescales are highly clinically relevant showing the potential to tune drug delivery during the healing process and offer an efficient means to improve patient outcomes.
在一些视网膜脱离的病例中，治疗可能需要去除眼睛内的玻璃体并用硅油代替，以帮助视网膜愈合。硅油的插入提供了将药物输送到眼睛内部的机会；然而，药物在硅油中的溶解度很差，并且从这种疏水性药物储库中释放不容易控制。在这里，我们设计了一系列统计接枝共聚物，在侧链中包含二甲基硅氧烷和乙二醇重复单元，允许短链的聚乙二醇溶解在硅油中，并提供氢键接受位点与酸性功能药物分子相互作用。我们的假设包括这种相互作用有可能延迟/控制药物释放，并且聚合物的结构和组成在目标聚合物与硅油的混溶性中发挥作用。这种策略已经使用布洛芬和全反式视黄酸成功地得到了证明；这两种药物都具有抗炎和抗增殖活性。在证明共聚物对视网膜色素上皮细胞无毒后，使用放射性化学方法研究药物释放表明，线性接枝共聚物的存在可以将布洛芬的释放延长三倍以上（从 3 天延长至>9 天），而全反式视黄酸从硅油相的释放延长至>72 天。这些时间尺度具有高度的临床相关性，表明有可能在愈合过程中调整药物输送，并提供一种有效的方法来改善患者的预后。
