Polymer Technology, Department of Chemical and Metallurgical Engineering, School of Chemical Engineering, Aalto University, Finland.
Polymer Technology, Department of Chemical and Metallurgical Engineering, School of Chemical Engineering, Aalto University, Finland.
Eur J Pharm Biopharm. 2020 May;150:33-42. doi: 10.1016/j.ejpb.2020.02.015. Epub 2020 Mar 3.
Photo-crosslinkable polymers have a great potential for the delivery of sensitive drugs. They allow preparation of drug releasing devices by photo-crosslinking, thus avoiding high processing temperatures. In this study, the hydrolysis behavior and drug release of three different photo-crosslinkable poly(ether anhydride)s and one poly(ester anhydride) were investigated. Three-arm poly(ethylene glycol) or polycaprolactone was reacted with succinic anhydride to obtain carboxylated macromers, and further functionalized with methacrylic anhydride to form methacrylated marcromers with anhydride linkages. The synthetized macromers were used to prepare photo-crosslinked matrices with different hydrolytic degradation times for active agent release purposes. The hydrolysis was clearly pH-sensitive: polymer networks degraded slowly in acidic conditions, and degradation rate increased as the pH shifted towards basic conditions. Drug release was studied with two water-soluble model drugs lidocaine (234 mol/g) and vitamin B (1355 g/mol). Vitamin B was released mainly due to polymer network degradation, whereas smaller molecule lidocaine was released also through diffusion and swelling of polymer network. Only a small amount of vitamin B was released in acidic conditions (pH 1.3 and pH 2.1). These polymers have potential in colon targeted drug delivery as the polymer could protect sensitive drugs from acidic conditions in the stomach, and the drug would be released as the conditions change closer to neutral pH in the intestine.
光交联聚合物在输送敏感药物方面具有巨大的潜力。它们可以通过光交联制备药物释放装置，从而避免使用高温处理。在这项研究中，研究了三种不同的光交联聚（醚酐）和一种聚（酯酐）的水解行为和药物释放。三臂聚（乙二醇）或聚己内酯与琥珀酸酐反应得到羧基化大分子单体，然后与甲基丙烯酰酐进一步反应，形成带有酸酐键的甲基丙烯酰化大分子单体。合成的大分子单体用于制备具有不同水解降解时间的光交联基质，以实现活性药物释放。水解明显对 pH 敏感：聚合物网络在酸性条件下缓慢降解，随着 pH 向碱性条件转变，降解速率增加。用两种水溶性模型药物利多卡因（234 mol/g）和维生素 B（1355 g/mol）研究了药物释放。维生素 B 的释放主要是由于聚合物网络的降解，而小分子利多卡因的释放也通过聚合物网络的扩散和溶胀实现。在酸性条件下（pH 1.3 和 pH 2.1）仅释放少量维生素 B。这些聚合物在结肠靶向药物输送中有应用潜力，因为聚合物可以保护敏感药物免受胃内酸性条件的影响，并且随着条件接近肠道中接近中性 pH 的变化，药物将被释放。
