283e pH-Sensitive Poly (N,N-Dimethylaminoethyl Methacrylate / 2-Hydroxyethyl Methacrylate Nanoparticles) as Efficient Drug Carriers

Jin-Oh You and Debra T. Auguste. School of Engineering and Applied Sciences, Harvard University, 40 Oxford St. ESL 224, Cambridge, MA 02138

For the triggered release of paclitaxel within a tomor microenvironment, pH-sensitive poly (N,N-dimethylaminoethyl methacrylate (DMAEMA) / 2-hydroxyethyl methacrylate (HEMA)) nanoparticles were prepared. Tumors exhibit a lower exracellular 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 hour incubation at 37 ºC. After adjusting to pH 6.8, 25% of the payload is released within 2 hours. Cell viability studies indicate that pH-sensitive DMAEMA/HEMA nanoparticles are biocompatible and may be used as an efficient, feedback-regulated drug delivery carrier.