Poly(ethylene oxide)-modified poly(beta-amino ester) nanoparticles as a pH-sensitive system for tumor-targeted delivery of hydrophobic drugs: part 3. Therapeutic efficacy and safety studies in ovarian cancer xenograft model
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The objective of this study was to evaluate the anti-tumor efficacy and lack of systemic toxicity of paclitaxel when administered in pH-sensitive poly(ethylene oxide) (PEO)-modified poly(beta-amino ester) (PbAE) nanoparticles in mice bearing human ovarian adenocarcinoma (SKOV-3) xenograft.
Paclitaxel-encapsulated PEO-modified PbAE (PEO–PbAE) nanoparticles were prepared by the solvent displacement method. PEO-modified poly(epsilon-caprolactone) (PCL) (PEO–PCL) nanoparticles were used as a non pH-responsive control formulation. Efficacy studies were conducted in SKOV-3 tumor-bearing athymic (Nu/Nu) mice at an equivalent paclitaxel dose of 20 mg/kg with the control and nanoparticle formulations. Safety of the drug when administered in the control and nanoparticle formulation was determined from blood cell counts and changes in body weight of the animals.
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 administration of paclitaxel in these formulations, the tumor growth was inhibited significantly. Both of the formulated nanoparticles tested have shown improved therapeutic efficacy as compared to the paclitaxel aqueous solution. Additionally, significantly lower toxicity profile of paclitaxel was observed with PEO-modified nanoparticles as compared to the aqueous solution formulation
PEO-modified PbAE nanoparticles are a unique pH-sensitive drug delivery system that elicits enhanced efficacy and safety profile in solid tumor therapy.
KeywordsBiodegradable pH sensitive Nanoparticles Poly(beta-amino ester) Poly(epsilon-caprolactone) Tumor targeting Efficacy Safety
This study was supported by grants R01-CA095522 and R01-CA119617 from the National Cancer Institute of the National Institutes of Health. The authors thank Professor Robert Campbell for the particle size and zeta potential measurements. In addition, Dr. Michael Seiden and Dr. Duan Zhenfeng of Massachusetts General Hospital are thanked for providing the SKOV-3 tumor cell lines.
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