You Jin-Oh, Auguste Debra T
School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Biomaterials. 2008 Apr;29(12):1950-7. doi: 10.1016/j.biomaterials.2007.12.041. Epub 2008 Feb 5.
pH-Sensitive poly(N,N-dimethylaminoethyl methacrylate (DMAEMA)/2-hydroxyethyl methacrylate (HEMA)) nanoparticles were prepared for the triggered release of paclitaxel within a tumor microenvironment. Tumors exhibit a lower extracellular pH than normal tissues. We show that paclitaxel release from DMAEMA/HEMA particles can be actively triggered by small, physiological changes in pH (within 0.2-0.6 pH units). Monodispersed nanoparticles were synthesized by forming an O/W emulsion followed by photopolymerization. Particles were characterized by transmission electron microscopy, dynamic light scattering, electrophoresis, and cytotoxicity. High release rates and swelling ratios are achieved at low pH, low crosslinking density, and high content of DMAEMA. Paclitaxel release is limited to 9% of the payload at pH 7.4 after a 2-h incubation at 37 degrees C. After adjusting to pH 6.8, 25% of the payload is released within 2h. Cell viability studies indicate that pH-sensitive DMAEMA/HEMA nanoparticles are not cytotoxic and may be used as an efficient, feedback-regulated drug delivery carrier.
制备了对pH敏感的聚（N，N - 二甲基氨基乙基甲基丙烯酸酯（DMAEMA）/甲基丙烯酸2 - 羟乙酯（HEMA））纳米颗粒，用于在肿瘤微环境中触发紫杉醇的释放。肿瘤细胞外的pH值低于正常组织。我们发现，pH值发生微小的生理变化（在0.2 - 0.6个pH单位范围内）就能主动触发DMAEMA/HEMA颗粒释放紫杉醇。通过形成水包油乳液然后进行光聚合反应合成了单分散纳米颗粒。通过透射电子显微镜、动态光散射、电泳和细胞毒性对颗粒进行了表征。在低pH值、低交联密度和高DMAEMA含量的条件下，可实现高释放率和高溶胀率。在37℃孵育2小时后，在pH 7.4时，紫杉醇的释放量限制在载药量的9%。将pH值调至6.8后，2小时内25%的载药量被释放。细胞活力研究表明，对pH敏感的DMAEMA/HEMA纳米颗粒无细胞毒性，可作为一种高效的、反馈调节的药物递送载体。
