Stable and efficient delivery of docetaxel by micelle-encapsulation using a tripodal cyclotriphosphazene amphiphile

Yong Joo Jun; Vithal B. Jadhav; Jee Hyon Min; Jin Xin Cui; Song Wha Chae; Jong Min Choi; In Sun Kim; Soo Jin Choi; Hwa Jeong Lee; Youn Soo Sohn

doi:10.1016/j.ijpharm.2011.10.052

Stable and efficient delivery of docetaxel by micelle-encapsulation using a tripodal cyclotriphosphazene amphiphile

Yong Joo Jun
, Vithal B. Jadhav
, Jee Hyon Min
, Jin Xin Cui
, Song Wha Chae
, Jong Min Choi
, In Sun Kim
, Soo Jin Choi
, Hwa Jeong Lee
, Youn Soo Sohn

Department of Pharmaceutical Sciences

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

36 Scopus citations

Abstract

Docetaxel micelle-encapsulated by a tripodal cyclotriphosphazene amphiphilile [NP(PEG750)(GlyPheLeu) ₂Et] ₃ (CP750) exhibited outstanding drug-loaded micelle stability in aqueous solution compared with the polymeric micelles assembled from linear block copolymers. Furthermore, docetaxel micelle-encapsulated by CP750 is obtainable in solvent free powder form, which is immediately soluble in any aqueous media including saline and PBS and very stable to photo-degradation even in the room light at room temperature. Although docetaxel micelle-encapsulated by CP750 did not display highly improved pharmacokinetic profile compared with Taxotere® currently in clinical use, its in vivo xenograft trials exhibited excellent antitumor efficacy by showing complete tumor regression against the breast cancer cells (MDA-MB-231) at a lower dose of 5 mg/kg and better efficacy against gastric cancer cells (MKN-28) compared with Taxotere®. Furthermore, according to the comparative acute toxicity study, toxicities associated with Taxotere® may be remarkably reduced by micelle-encapsulation of docetaxel using CP750, which afforded a much higher LD ₅₀ value of 75 mg/kg compared with 28 mg/kg of docetaxel in Taxotere®. Thus docetaxel micelle-encapsulated by CP750 has entered the stage of preclinical studies.

Original language	English
Pages (from-to)	374-380
Number of pages	7
Journal	International Journal of Pharmaceutics
Volume	422
Issue number	1-2
DOIs	https://doi.org/10.1016/j.ijpharm.2011.10.052
State	Published - 17 Jan 2012

Bibliographical note

Funding Information:
This work was supported by National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MEST) (SRC Program: 2011-0001340, NCRC Program: 2011-0006244, 2011-0013493), by a Korean Research Foundation Grant ( KRF-2004-005-C00090 ), by Seoul R & BD Program (10816), and by the Ewha Global Top 5 Grant 2011 of Ewha Womans University.

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Anticancer drug
Cyclotriphosphazene
Docetaxel
Micelle
Taxane

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10.1016/j.ijpharm.2011.10.052

Cite this

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title = "Stable and efficient delivery of docetaxel by micelle-encapsulation using a tripodal cyclotriphosphazene amphiphile",

abstract = "Docetaxel micelle-encapsulated by a tripodal cyclotriphosphazene amphiphilile [NP(PEG750)(GlyPheLeu) 2Et] 3 (CP750) exhibited outstanding drug-loaded micelle stability in aqueous solution compared with the polymeric micelles assembled from linear block copolymers. Furthermore, docetaxel micelle-encapsulated by CP750 is obtainable in solvent free powder form, which is immediately soluble in any aqueous media including saline and PBS and very stable to photo-degradation even in the room light at room temperature. Although docetaxel micelle-encapsulated by CP750 did not display highly improved pharmacokinetic profile compared with Taxotere{\textregistered} currently in clinical use, its in vivo xenograft trials exhibited excellent antitumor efficacy by showing complete tumor regression against the breast cancer cells (MDA-MB-231) at a lower dose of 5 mg/kg and better efficacy against gastric cancer cells (MKN-28) compared with Taxotere{\textregistered}. Furthermore, according to the comparative acute toxicity study, toxicities associated with Taxotere{\textregistered} may be remarkably reduced by micelle-encapsulation of docetaxel using CP750, which afforded a much higher LD 50 value of 75 mg/kg compared with 28 mg/kg of docetaxel in Taxotere{\textregistered}. Thus docetaxel micelle-encapsulated by CP750 has entered the stage of preclinical studies.",

keywords = "Anticancer drug, Cyclotriphosphazene, Docetaxel, Micelle, Taxane",

author = "Jun, \{Yong Joo\} and Jadhav, \{Vithal B.\} and Min, \{Jee Hyon\} and Cui, \{Jin Xin\} and Chae, \{Song Wha\} and Choi, \{Jong Min\} and Kim, \{In Sun\} and Choi, \{Soo Jin\} and Lee, \{Hwa Jeong\} and Sohn, \{Youn Soo\}",

note = "Funding Information: This work was supported by National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MEST) (SRC Program: 2011-0001340, NCRC Program: 2011-0006244, 2011-0013493), by a Korean Research Foundation Grant ( KRF-2004-005-C00090 ), by Seoul R \& BD Program (10816), and by the Ewha Global Top 5 Grant 2011 of Ewha Womans University. ",

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doi = "10.1016/j.ijpharm.2011.10.052",

language = "English",

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AU - Jun, Yong Joo

AU - Jadhav, Vithal B.

AU - Min, Jee Hyon

AU - Cui, Jin Xin

AU - Chae, Song Wha

AU - Choi, Jong Min

AU - Kim, In Sun

AU - Choi, Soo Jin

AU - Lee, Hwa Jeong

AU - Sohn, Youn Soo

N1 - Funding Information: This work was supported by National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MEST) (SRC Program: 2011-0001340, NCRC Program: 2011-0006244, 2011-0013493), by a Korean Research Foundation Grant ( KRF-2004-005-C00090 ), by Seoul R & BD Program (10816), and by the Ewha Global Top 5 Grant 2011 of Ewha Womans University.

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N2 - Docetaxel micelle-encapsulated by a tripodal cyclotriphosphazene amphiphilile [NP(PEG750)(GlyPheLeu) 2Et] 3 (CP750) exhibited outstanding drug-loaded micelle stability in aqueous solution compared with the polymeric micelles assembled from linear block copolymers. Furthermore, docetaxel micelle-encapsulated by CP750 is obtainable in solvent free powder form, which is immediately soluble in any aqueous media including saline and PBS and very stable to photo-degradation even in the room light at room temperature. Although docetaxel micelle-encapsulated by CP750 did not display highly improved pharmacokinetic profile compared with Taxotere® currently in clinical use, its in vivo xenograft trials exhibited excellent antitumor efficacy by showing complete tumor regression against the breast cancer cells (MDA-MB-231) at a lower dose of 5 mg/kg and better efficacy against gastric cancer cells (MKN-28) compared with Taxotere®. Furthermore, according to the comparative acute toxicity study, toxicities associated with Taxotere® may be remarkably reduced by micelle-encapsulation of docetaxel using CP750, which afforded a much higher LD 50 value of 75 mg/kg compared with 28 mg/kg of docetaxel in Taxotere®. Thus docetaxel micelle-encapsulated by CP750 has entered the stage of preclinical studies.

AB - Docetaxel micelle-encapsulated by a tripodal cyclotriphosphazene amphiphilile [NP(PEG750)(GlyPheLeu) 2Et] 3 (CP750) exhibited outstanding drug-loaded micelle stability in aqueous solution compared with the polymeric micelles assembled from linear block copolymers. Furthermore, docetaxel micelle-encapsulated by CP750 is obtainable in solvent free powder form, which is immediately soluble in any aqueous media including saline and PBS and very stable to photo-degradation even in the room light at room temperature. Although docetaxel micelle-encapsulated by CP750 did not display highly improved pharmacokinetic profile compared with Taxotere® currently in clinical use, its in vivo xenograft trials exhibited excellent antitumor efficacy by showing complete tumor regression against the breast cancer cells (MDA-MB-231) at a lower dose of 5 mg/kg and better efficacy against gastric cancer cells (MKN-28) compared with Taxotere®. Furthermore, according to the comparative acute toxicity study, toxicities associated with Taxotere® may be remarkably reduced by micelle-encapsulation of docetaxel using CP750, which afforded a much higher LD 50 value of 75 mg/kg compared with 28 mg/kg of docetaxel in Taxotere®. Thus docetaxel micelle-encapsulated by CP750 has entered the stage of preclinical studies.

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KW - Cyclotriphosphazene

KW - Docetaxel

KW - Micelle

KW - Taxane

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AN - SCOPUS:84655164349

SN - 0378-5173

VL - 422

SP - 374

EP - 380

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

IS - 1-2

ER -

Stable and efficient delivery of docetaxel by micelle-encapsulation using a tripodal cyclotriphosphazene amphiphile

Abstract

Bibliographical note

UN SDGs

Keywords

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