Mixed pH-sensitive polymeric micelles for combination drug delivery

Younsoo Bae; Adam W.G. Alani; Nicole C. Rockich; T. S.Z.Chung Lai; Glen S. Kwon

doi:10.1007/s11095-010-0234-3

Mixed pH-sensitive polymeric micelles for combination drug delivery

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

Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

51 Scopus citations

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.

Original language	English
Pages (from-to)	2421-2432
Number of pages	12
Journal	Pharmaceutical Research
Volume	27
Issue number	11
DOIs	https://doi.org/10.1007/s11095-010-0234-3
State	Published - Nov 2010

Bibliographical note

Funding Information:
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.

Funding

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.

Funders	Funder number
Kentucky Lung Cancer Research Program
National Institutes of Health (NIH)	R01 AI-43346-08
National Institute of Allergy and Infectious Diseases	R01AI043346

Keywords

combination chemotherapy
drug delivery
mixed micelles
pH-controlled release
polymeric micelles

ASJC Scopus subject areas

Biotechnology
Molecular Medicine
Pharmacology
Pharmaceutical Science
Organic Chemistry
Pharmacology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s11095-010-0234-3

Cite this

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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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author = "Younsoo Bae and Alani, {Adam W.G.} and Rockich, {Nicole C.} and Lai, {T. S.Z.Chung} and Kwon, {Glen S.}",

note = "Funding Information: 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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AU - Alani, Adam W.G.

AU - Rockich, Nicole C.

AU - Lai, T. S.Z.Chung

AU - Kwon, Glen S.

N1 - Funding Information: 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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N2 - 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.

AB - 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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KW - pH-controlled release

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Mixed pH-sensitive polymeric micelles for combination drug delivery

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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