Cancer Chemotherapy and Pharmacology

, Volume 59, Issue 4, pp 477–484 | Cite as

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

  • Harikrishna Devalapally
  • Dinesh Shenoy
  • Steven Little
  • Robert Langer
  • Mansoor Amiji
Original Article

Abstract

Purpose

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.

Methods

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.

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 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

Conclusion

PEO-modified PbAE nanoparticles are a unique pH-sensitive drug delivery system that elicits enhanced efficacy and safety profile in solid tumor therapy.

Keywords

Biodegradable pH sensitive Nanoparticles Poly(beta-amino ester) Poly(epsilon-caprolactone) Tumor targeting Efficacy Safety 

Notes

Acknowledgments

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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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Harikrishna Devalapally
    • 1
  • Dinesh Shenoy
    • 1
    • 3
  • Steven Little
    • 2
    • 4
  • Robert Langer
    • 2
  • Mansoor Amiji
    • 1
  1. 1.Department of Pharmaceutical Sciences, School of PharmacyNortheastern UniversityBostonUSA
  2. 2.Department of Chemical EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  3. 3.Novavax, Inc.MalvernUSA
  4. 4.Department of Chemical EngineeringUniversity of PittsburghPittsburghUSA

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