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Mixed pH-Sensitive Polymeric Micelles for Combination Drug Delivery

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ABSTRACT

Purpose

To prepare mixed polymeric micelles that can carry two different drugs, doxorubicin (DOX) and 17-hydroxyethylamino-17-demethoxygeldanamycin (GDM-OH), for combination cancer chemotherapy.

Methods

The pH-sensitive micelles were prepared from poly(ethylene glycol)-poly(aspartate hydrazide) block copolymers to which either DOX or GDM-OH is conjugated through acid-labile hydrazone bond (individual micelles). Mixed micelles were formed not only by simply mixing two different individual micelles in aqueous solutions (aqueous mixed micelles) but also by evaporating organic solvents from the organic/aqueous mixed solvents in which two block copolymers possessing different drugs were dissolved homogeneously (organic mixed micelles). Particle size measurements, pH-dependent drug release tests, cytotoxicity assays and western blot analysis were subsequently conducted.

Results

Individual and aqueous/organic mixed micelles showed clinically relevant particle size (<100 nm) and pH-dependent drug release patterns. Mixed polymer micelles suppress cancer cell growth effectively in a drug concentration, mixing method and schedule-dependent way.

Conclusion

Combination chemotherapy using polymeric micelles seems to minimize a schedule-dependent change in combination drug efficacy in comparison to drug combination using DMSO formulations.

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ACKNOWLEDGEMENTS

This work was partially supported by National Institutes of Health grant R01 AI-43346-08. Y.B. acknowledges research support provided by the Kentucky Lung Cancer Research Program.

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Authors and Affiliations

  1. Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, Lexington, Kentucky, 40536-0596, USA

    Younsoo Bae

  2. Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, Wisconsin, 53705-2222, USA

    Adam W. G. Alani, Nicole C. Rockich, T. S. Z. Chung Lai & Glen S. Kwon

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  1. Younsoo Bae
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  2. Adam W. G. Alani
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  3. Nicole C. Rockich
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  4. T. S. Z. Chung Lai
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  5. Glen S. Kwon
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Correspondence to Younsoo Bae.

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Bae, Y., Alani, A.W.G., Rockich, N.C. et al. Mixed pH-Sensitive Polymeric Micelles for Combination Drug Delivery. Pharm Res 27, 2421–2432 (2010). https://doi.org/10.1007/s11095-010-0234-3

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  • DOI: https://doi.org/10.1007/s11095-010-0234-3

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