Aydin Derya, Kizilel Seda
Department of Chemical and Biological Engineering, Koc University Sariyer Istanbul Turkey 34450
RSC Adv. 2018 May 18;8(33):18216-18226. doi: 10.1039/c8ra01460d. eCollection 2018 May 17.
We report here a method for the synthesis of a unique hybrid gel system for the sustained delivery of P2X7 receptor (P2X7R) antagonist. P2X7R has been reported as a key mediator in inflammatory processes and controlled delivery of this molecule would be critical for the treatment of inflammatory arthritis. The hybrid gel designed here for the sustained delivery of P2X7R antagonists is based on crosslinked hydrophobic styrene-butadiene-styrene (SBS) polymer as a continuous network, where hydrogel particles prepared with hydrophilic poly(ethylene glycol) (PEG) were embedded into this system. PEG hydrogel particle-incorporated SBS gels were characterized through electron microscopy, water contact angle observations, and strong mechanical properties were confirmed through nanoindentation measurements. The release of P2X7R antagonist from these hybrid hydrogel-elastomer system demonstrated a sustained drug release profile up to 28 days at physiological pH, which was not observed in earlier reports. We obtained drug release percentages ranging from 49.72% to 93.04% which indicated the tunability of release through SBS crosslinking and hydrophilic/hydrophobic nature of SBS. This tunability is significant to achieve simultaneous improvements in drug efficacy with reduced side effects. CellTiter-Glo luminescence measurements using human kidney cells revealed that these networks are non-toxic and highly biocompatible with percent cell viabilities of higher than 85%. The approach presented here with crosslinked, amphiphilic and elastic SBS gel systems is not only promising for extended release of P2X7R antagonist but could also allow for incorporation of different molecules so that simultaneous/sequential and extended release profiles for therapeutic molecules could be achieved.
我们在此报告一种合成独特混合凝胶系统的方法，用于持续递送P2X7受体（P2X7R）拮抗剂。P2X7R已被报道为炎症过程中的关键介质，对该分子的可控递送对于炎性关节炎的治疗至关重要。此处设计的用于持续递送P2X7R拮抗剂的混合凝胶基于交联的疏水苯乙烯 - 丁二烯 - 苯乙烯（SBS）聚合物作为连续网络，其中用亲水性聚乙二醇（PEG）制备的水凝胶颗粒嵌入该系统。通过电子显微镜对掺入PEG水凝胶颗粒的SBS凝胶进行了表征，通过水接触角观察进行了表征，并通过纳米压痕测量证实了其强大的机械性能。这些混合水凝胶 - 弹性体系统中P2X7R拮抗剂的释放在生理pH下显示出长达28天的持续药物释放曲线，这在早期报告中未观察到。我们获得的药物释放百分比范围为49.72%至93.04%，这表明通过SBS交联以及SBS的亲水/疏水性质可调节释放。这种可调节性对于在降低副作用的同时提高药物疗效具有重要意义。使用人肾细胞进行的CellTiter - Glo发光测量表明，这些网络无毒且具有高度生物相容性，细胞活力百分比高于85%。此处提出的具有交联、两亲性和弹性SBS凝胶系统的方法不仅有望实现P2X7R拮抗剂的延长释放，还可以掺入不同分子，从而实现治疗分子的同时/顺序和延长释放曲线。
