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Research ArticleRESEARCH

Evaluation of Microparticles Containing Doxorubicin Suitable for Aerosol Delivery to the Lungs

Youqin Tian, Melvin E. Klegerman and Anthony J. Hickey
PDA Journal of Pharmaceutical Science and Technology September 2004, 58 (5) 266-275;
Youqin Tian
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Melvin E. Klegerman
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Anthony J. Hickey
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Abstract

The efficacy of microparticulate systems containing anticancer agents may be assessed in vitro prior to evaluation of the effects of targeted and controlled drug release on tumor growth. Particles prepared in a size range suitable for aerosol delivery to the lungs (1–5 μm) would be useful in the treatment of locally occurring tumors. Bovine serum albumin microparticles containing doxorubicin (2.6-μm median diameter) were prepared by an emulsion technique with thermal stabilization. Dialysis was used to assess drug release in citrate phosphate buffer pH 4.0 and phosphate buffer pH 7.4, at 37 °C. Sixty percent of the doxorubicin load was released in a 10-h burst at pH 4.0. An additional 20% was released up to 70 h. Fifty percent of the drug was released in 70 h at pH 7.4. S180 murine sarcoma cells were incubated with doxorubicin in solution and in microparticle suspension for 24, 48, and 72 h to evaluate cytotoxicity. Viable cells were recovered in smaller numbers following treatment with doxorubicin microparticles than following treatment with doxorubicin solution. The action of doxorubicin on growth of S180 murine sarcoma cells was enhanced in vitro by delivery in microparticles. A four-fold reduction in the effective dose, at which the rate of cell death exceeds replication, was observed for microparticles (5 μg/ml) than for doxorubicin alone (20 μg/ml). Therefore, the doxorubicin microparticles exhibit potential for greater therapeutic effect than drug alone when evaluated in vitro. Further studies are required to demonstrate the aerodynamic properties of these particles and efficacy in an in vivo tumor model.

  • doxorubicin
  • albumin
  • microparticles
  • sarcoma
  • aerosol
  • lungs

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PDA Journal of Pharmaceutical Science and Technology
Vol. 58, Issue 5
September/October 2004
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Evaluation of Microparticles Containing Doxorubicin Suitable for Aerosol Delivery to the Lungs
Youqin Tian, Melvin E. Klegerman, Anthony J. Hickey
PDA Journal of Pharmaceutical Science and Technology Sep 2004, 58 (5) 266-275;

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Evaluation of Microparticles Containing Doxorubicin Suitable for Aerosol Delivery to the Lungs
Youqin Tian, Melvin E. Klegerman, Anthony J. Hickey
PDA Journal of Pharmaceutical Science and Technology Sep 2004, 58 (5) 266-275;
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