Dendron-based micelles for topical delivery of endoxifen: A potential chemo-preventive medicine for breast cancer

Yang Yang, Ryan M. Pearson, Oukseub Lee, Chan Woo Lee, Robert T. Chatterton, Seema A. Khan, Seungpyo Hong

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Endoxifen (EDX) is an active metabolite of tamoxifen that has been proven effective in the prevention and treatment of estrogen-positive breast cancer; however, oral administration of tamoxifen often causes severe side effects. Here, the topical delivery of EDX is explored using polymeric micelles to achieve localized drug delivery with potentially minimal side effects. EDX is encapsulated into dendron micelles (DM) with various surface groups (-NH 2, -COOH, or -Ac) and into cationic liposomes as a control. End-group modification significantly affects the drug loading, where the DM-COOH micelles allow the most efficient encapsulation. Furthermore, unlike the burst release from the liposomes, all DMs show sustained release of EDX over 6 days. Each formulation is evaluated for its potential to deliver EDX across the skin layers. DMs substantially enhance the permeation of EDX through both mouse (up to 20-fold) and human (up to 4-fold) skin samples relative to ethanol, a chemical penetration enhancer. Franz diffusion cell experiments reveal that DM-COOH induces the highest flux of EDX among all groups. The enhanced drug loading, controlled release profiles, and enhanced skin permeation all demonstrate that DMs are a useful platform for the topical delivery of EDX, offering a potential alternative administration route for chemoprevention. Surface-modified dendron micelles (DMs) are developed as a potential platform for the topical delivery of endoxifen (EDX). Skin permeation of EDX is highly dependent on the surface group of the DMs. In particular, carboxylated DMs exhibit significantly enhanced permeation of EDX through both mouse and human skin layers, offering a potential alternative administration route for chemoprevention.

Original languageEnglish
Pages (from-to)2442-2449
Number of pages8
JournalAdvanced Functional Materials
Volume24
Issue number17
DOIs
Publication statusPublished - 2014 May 2

Fingerprint

Bioelectric potentials
Micelles
medicine
breast
Medicine
delivery
micelles
cancer
Skin
Permeation
drugs
Liposomes
Tamoxifen
mice
4-hydroxy-N-desmethyltamoxifen
dendron
platforms
routes
estrogens
metabolites

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics

Cite this

Yang, Yang ; Pearson, Ryan M. ; Lee, Oukseub ; Lee, Chan Woo ; Chatterton, Robert T. ; Khan, Seema A. ; Hong, Seungpyo. / Dendron-based micelles for topical delivery of endoxifen : A potential chemo-preventive medicine for breast cancer. In: Advanced Functional Materials. 2014 ; Vol. 24, No. 17. pp. 2442-2449.
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abstract = "Endoxifen (EDX) is an active metabolite of tamoxifen that has been proven effective in the prevention and treatment of estrogen-positive breast cancer; however, oral administration of tamoxifen often causes severe side effects. Here, the topical delivery of EDX is explored using polymeric micelles to achieve localized drug delivery with potentially minimal side effects. EDX is encapsulated into dendron micelles (DM) with various surface groups (-NH 2, -COOH, or -Ac) and into cationic liposomes as a control. End-group modification significantly affects the drug loading, where the DM-COOH micelles allow the most efficient encapsulation. Furthermore, unlike the burst release from the liposomes, all DMs show sustained release of EDX over 6 days. Each formulation is evaluated for its potential to deliver EDX across the skin layers. DMs substantially enhance the permeation of EDX through both mouse (up to 20-fold) and human (up to 4-fold) skin samples relative to ethanol, a chemical penetration enhancer. Franz diffusion cell experiments reveal that DM-COOH induces the highest flux of EDX among all groups. The enhanced drug loading, controlled release profiles, and enhanced skin permeation all demonstrate that DMs are a useful platform for the topical delivery of EDX, offering a potential alternative administration route for chemoprevention. Surface-modified dendron micelles (DMs) are developed as a potential platform for the topical delivery of endoxifen (EDX). Skin permeation of EDX is highly dependent on the surface group of the DMs. In particular, carboxylated DMs exhibit significantly enhanced permeation of EDX through both mouse and human skin layers, offering a potential alternative administration route for chemoprevention.",
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Dendron-based micelles for topical delivery of endoxifen : A potential chemo-preventive medicine for breast cancer. / Yang, Yang; Pearson, Ryan M.; Lee, Oukseub; Lee, Chan Woo; Chatterton, Robert T.; Khan, Seema A.; Hong, Seungpyo.

In: Advanced Functional Materials, Vol. 24, No. 17, 02.05.2014, p. 2442-2449.

Research output: Contribution to journalArticle

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AB - Endoxifen (EDX) is an active metabolite of tamoxifen that has been proven effective in the prevention and treatment of estrogen-positive breast cancer; however, oral administration of tamoxifen often causes severe side effects. Here, the topical delivery of EDX is explored using polymeric micelles to achieve localized drug delivery with potentially minimal side effects. EDX is encapsulated into dendron micelles (DM) with various surface groups (-NH 2, -COOH, or -Ac) and into cationic liposomes as a control. End-group modification significantly affects the drug loading, where the DM-COOH micelles allow the most efficient encapsulation. Furthermore, unlike the burst release from the liposomes, all DMs show sustained release of EDX over 6 days. Each formulation is evaluated for its potential to deliver EDX across the skin layers. DMs substantially enhance the permeation of EDX through both mouse (up to 20-fold) and human (up to 4-fold) skin samples relative to ethanol, a chemical penetration enhancer. Franz diffusion cell experiments reveal that DM-COOH induces the highest flux of EDX among all groups. The enhanced drug loading, controlled release profiles, and enhanced skin permeation all demonstrate that DMs are a useful platform for the topical delivery of EDX, offering a potential alternative administration route for chemoprevention. Surface-modified dendron micelles (DMs) are developed as a potential platform for the topical delivery of endoxifen (EDX). Skin permeation of EDX is highly dependent on the surface group of the DMs. In particular, carboxylated DMs exhibit significantly enhanced permeation of EDX through both mouse and human skin layers, offering a potential alternative administration route for chemoprevention.

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