Ramanan Ram Mohan Kripa, Chellamuthu Prithiviraj, Tang Liping, Nguyen Kytai T
Utah State University, Logan, Utah 84322, USA.
Biotechnol Prog. 2006 Jan-Feb;22(1):118-25. doi: 10.1021/bp0501367.
To develop materials with improved controllability and specificity, we have investigated composite hydrogels with temperature-sensitive properties using photo cross-linking. Specifically, our novel composite materials are composed of nanoparticles made of poly(N-isopropylacrylamide) (PNIPAAm), temperature-sensitive hydrogels, and a photo cross-linker, poly(ethylene glycol) diacrylate (PEGDA). PNIPAAm particles were synthesized by emulsion polymerization and by varying concentration of four main factors: monomers (N-isopropylacrylamide), cross-linkers (N,N'-methylenebisacrylamide), surfactants (sodium dodecyl sulfate, SDS), and initiators (potassium persulfate). We found that the surfactant, SDS, was the most important factor affecting the particle size using the factorial design analysis. Additionally, both nano- and micro-PNIPAAm particles had excellent loading efficiency (>80% of the incubated bovine serum albumin (BSA)), and their release kinetics expressed an initial burst effect followed by a sustained release over time. Furthermore, BSA-loaded PNIPAAm nanoparticles were used to form three-dimensional gel networks by means of a photocuring process using a photo cross-linker, PEGDA, and a photoinitiator, Irgacure-2959 (I-2959). Results from scanning electron microscopy and in vitro BSA release studies from these hydrogels demonstrated that PNIPAAm nanoparticles were embedded inside the PEG polymeric matrix and the composite material was able to release BSA in response to changes in temperature. These PNIPAAm nanoparticle hydrogel networks may have advantages in applications of controlled drug delivery systems because of their temperature sensitivity and their ability of in situ photopolymerization to localize at the specific region in the body.
为了开发具有更好可控性和特异性的材料，我们研究了采用光交联法制备的具有温度敏感特性的复合水凝胶。具体而言，我们的新型复合材料由聚（N-异丙基丙烯酰胺）（PNIPAAm）制成的纳米颗粒、温度敏感水凝胶和光交联剂聚（乙二醇）二丙烯酸酯（PEGDA）组成。PNIPAAm颗粒通过乳液聚合合成，并通过改变四种主要因素的浓度来制备：单体（N-异丙基丙烯酰胺）、交联剂（N,N'-亚甲基双丙烯酰胺）、表面活性剂（十二烷基硫酸钠，SDS）和引发剂（过硫酸钾）。利用析因设计分析，我们发现表面活性剂SDS是影响粒径的最重要因素。此外，纳米和微米级的PNIPAAm颗粒均具有优异的负载效率（>80%的孵育牛血清白蛋白（BSA）），其释放动力学表现为初始突释效应，随后随时间持续释放。此外，负载BSA的PNIPAAm纳米颗粒通过使用光交联剂PEGDA和光引发剂Irgacure-2959（I-2959）的光固化过程形成三维凝胶网络。扫描电子显微镜结果以及这些水凝胶的体外BSA释放研究表明，PNIPAAm纳米颗粒嵌入在PEG聚合物基质中，并且该复合材料能够响应温度变化释放BSA。这些PNIPAAm纳米颗粒水凝胶网络由于其温度敏感性以及原位光聚合以定位在体内特定区域的能力，在可控药物递送系统的应用中可能具有优势。
