Cancer Chemother Pharmacol DOI 10.1007/s00280-006-0287-5 123 ORIGINAL ARTICLE Poly(ethylene oxide)-modiWed poly(beta-amino ester) nanoparticles as a pH-sensitive system for tumor-targeted delivery of hydrophobic drugs: part 3. Therapeutic eYcacy and safety studies in ovarian cancer xenograft model Harikrishna Devalapally · Dinesh Shenoy · Steven Little · Robert Langer · Mansoor Amiji Received: 29 March 2006 / Accepted: 21 June 2006  Springer-Verlag 2006 Abstract Purpose The objective of this study was to evaluate the anti-tumor eYcacy and lack of systemic toxicity of paclitaxel when administered in pH-sensitive poly(eth- ylene oxide) (PEO)-modiWed poly(beta-amino ester) (PbAE) nanoparticles in mice bearing human ovarian adenocarcinoma (SKOV-3) xenograft. Methods Paclitaxel-encapsulated PEO-modiWed PbAE (PEO–PbAE) nanoparticles were prepared by the sol- vent displacement method. PEO-modiWed poly(epsi- lon-caprolactone) (PCL) (PEO–PCL) nanoparticles were used as a non pH-responsive control formulation. EYcacy studies were conducted in SKOV-3 tumor- bearing athymic (Nu/Nu) mice at an equivalent paclit- axel dose of 20 mg/kg with the control and nanoparticle formulations. Safety of the drug when administered in the control and nanoparticle formulation was deter- mined from blood cell counts and changes in body weight of the animals. Results The formulated paclitaxel-containing PEO– PbAE and PEO–PCL nanoparticles had a particle size in the range of 100–200 nm and a surface charge of + 39.0 and ¡ 30.8 mV, respectively. After intravenous adminis- tration of paclitaxel in these formulations, the tumor growth was inhibited signiWcantly. Both of the formu- lated nanoparticles tested have shown improved thera- peutic eYcacy as compared to the paclitaxel aqueous solution. Additionally, signiWcantly lower toxicity proWle of paclitaxel was observed with PEO-modiWed nanoparti- cles as compared to the aqueous solution formulation Conclusion PEO-modiWed PbAE nanoparticles are a unique pH-sensitive drug delivery system that elicits enhanced eYcacy and safety proWle in solid tumor therapy. Keywords Biodegradable · pH sensitive · Nanoparticles · Poly(beta-amino ester) · Poly(epsilon-caprolactone) · Tumor targeting · EYcacy · Safety Introduction The major limitation with systemic cancer chemother- apy is the lack of tumor selectivity, resulting in severe dose-limiting adverse eVects. Furthermore, another serious limitation is the generation of multidrug-resis- tant tumor cells under the inXuence of long-term treat- ment, which results in suboptimal drug concentrations at the tumor site. It is, therefore, desirable to maintain a steady infusion of the drug into the tumor intersti- tium to accomplish continuous extermination of the H. Devalapally · D. Shenoy · M. Amiji (&) Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA 02115, USA e-mail: m.amiji@neu.edu S. Little · R. Langer Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA Present Address: D. Shenoy Novavax, Inc., 508 Lapp Road, Malvern, PA 19355, USA Present Address: S. Little Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USA