School of Pharmacy, Queen's University of Belfast, Northern Ireland, United Kingdom.
Eur J Pharm Biopharm. 2012 Nov;82(3):563-71. doi: 10.1016/j.ejpb.2012.07.019. Epub 2012 Aug 23.
Thermoresponsive polymeric platforms are used to optimise drug delivery in pharmaceutical systems and bioactive medical devices. However, the practical application of these systems is compromised by their poor mechanical properties. This study describes the design of thermoresponsive semi-interpenetrating polymer networks (s-IPNs) based on cross-linked p(NIPAA) or p(NIPAA-co-HEMA) hydrogels containing poly(ε-caprolactone) designed to address this issue. Using DSC, the lower critical solution temperature of the co-polymer and p(NIPAA) matrices were circa 34°C and 32°C, respectively. PCL was physically dispersed within the hydrogel matrices as confirmed using confocal scanning laser microscopy and DSC and resulted in marked changes in the mechanical properties (ultimate tensile strength, Young's modulus) without adversely compromising the elongation properties. P(NIPAA) networks containing dispersed PCL exhibited thermoresponsive swelling properties following immersion in buffer (pH 7), with the equilibrium-swelling ratio being greater at 20°C than 37°C and greatest for p(NIPAA)/PCL systems at 20°C. The incorporation of PCL significantly lowered the equilibrium swelling ratio of the various networks but this was not deemed practically significant for s-IPNs based on p(NIPAA). Thermoresponsive release of metronidazole was observed from s-IPN composed of p(NIPAA)/PCL at 37°C but not from p(NIPAA-co-HEMA)/PCL at this temperature. In all other platforms, drug release at 20°C was significantly similar to that at 37°C and was diffusion controlled. This study has uniquely described a strategy by which thermoresponsive drug release may be performed from polymeric platforms with highly elastic properties. It is proposed that these materials may be used clinically as bioactive endotracheal tubes, designed to offer enhanced resistance to ventilator associated pneumonia, a clinical condition associated with the use of endotracheal tubes where stimulus responsive drug release from biomaterials of significant mechanical properties would be advantageous.
温敏聚合物平台被用于优化药物输送的药物制剂系统和生物活性的医疗设备。然而,这些系统的实际应用受到其机械性能差的影响。本研究描述了基于互穿聚合物网络(s-IPN)的设计热响应半交联 p(NIPAA)或 p(NIPAA-co-HEMA)水凝胶含有聚(ε-己内酯)旨在解决这个问题。使用差示扫描量热法,共聚物和 p(NIPAA)基质的低临界溶液温度分别约为 34°C 和 32°C。PCL 是物理分散在水凝胶基质中,如共聚焦扫描激光显微镜和差示扫描量热法证实,并导致在机械性能的显著变化(极限拉伸强度,杨氏模量)而不会不利地影响伸长率性能。含有分散 PCL 的 p(NIPAA)网络在缓冲液(pH7)中表现出温敏溶胀性能,在 20°C 下的平衡溶胀比大于 37°C,在 20°C 下 p(NIPAA)/PCL 系统最大。PCL 的掺入显著降低了各种网络的平衡溶胀比,但对于基于 p(NIPAA)的 s-IPN 这不被认为具有实际意义。在 37°C 下观察到 s-IPN 组成的甲硝唑的温敏释放,但在该温度下 p(NIPAA-co-HEMA)/PCL 则没有。在所有其他平台中,在 20°C 下的药物释放与在 37°C 下的药物释放显著相似,并且是扩散控制的。本研究独特地描述了一种策略,通过该策略可以从具有高弹性性质的聚合物平台进行温敏药物释放。据提议,这些材料可以在临床上用作生物活性的气管内管,旨在提供对呼吸机相关性肺炎的增强抗性,这是与使用气管内管相关的临床情况,其中生物材料的刺激响应性药物释放具有显著的机械性能将是有利的。