Summary: Feedback-regulated paclitaxel delivery based on
Jin-Oh You, Debra T. Auguste*
School of Engineering and Applied Sciences, Harvard University, 29 Oxford Street, Pierce 317, Cambridge, MA 02138, USA
Received 17 October 2007; accepted 23 December 2007
Available online 5 February 2008
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 0.2e0.6 pH
units). Monodispersed nanoparticles were synthesized by forming an O/W emulsion followed by photopolymerization. Particles were charac-
terized 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
C. After adjusting to pH 6.8, 25% of the payload is released within 2 h. 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.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: pH-Sensitive nanoparticle; DMAEMA; HEMA; Paclitaxel; Controlled release; Cancer therapeutic