Article
  • Docetaxel Nanocrystals Producedvia an Amorphous Precursor
  • Insil Choi, Hee-Jin Kim, Kab Sig Kim*, Yong Suk Jin*, Eun Yong Lee*, Joo Won Park*, Young-Je Kwark**, Yun Sang Lee***, Jae Hyun Jeong , and Il Won Kim

  • Department of Chemical Engineering, Soongsil University, Seoul 06978, Korea
    *Bio-Synectics, Inc., Seoul 08501, Korea
    **Department of Organic Materials and Fiber Engineering, Soongsil University, Seoul 06978, Korea
    ***Department of Physics, Soongsil University, Seoul 06978, Korea

  • 무정형 전구체를 통한 도세탁셀 나노결정의 형성
  • 최인실 ·김희진 ·김갑식* ·진용석* ·이은용* ·박주원* ·곽영제** ·이윤상*** ·정재현 ·김일원

  • 숭실대학교 화학공학과, *(주)바이오시네틱스, **숭실대학교 유기신소재·파이버공학과, ***숭실대학교 물리학과

  • Reproduction, stored in a retrieval system, or transmitted in any form of any part of this publication is permitted only by written permission from the Polymer Society of Korea.

Abstract

Docetaxel is an anti-cancer medication in the taxane family administered intravenously due to its low aqueous solubility and gastrointestinal permeability. The current commercial formulation contains a substantial amount of solubilizing excipients that could cause systemic anaphylaxis and cardiovascular side effects. Nanocrystal formulation is an ideal alternative to circumvent excipient-related problems, and it could also take advantage of the defective vascular architecture of solid tumors through enhanced permeability and retention. In the present study, we combined phase separation and high-pressure homogenization processes to generate docetaxel nanocrystals (ca. 200 nm). The initial phase separation of docetaxel from the solution with 1-tetradecanol produced an amorphous nano-precursor in the presence of poly(vinyl pyrrolidone), which was subsequently transformed into the nanocrystals during the high-pressure homogenization. The nanocrystals exhibited a promising anti-cancer effect with minimal damage to normal tissue when tested with a chicken chorioallantoic membrane model.


Taxane계 항암제인 도세탁셀은 낮은 용해도와 투과도로 인해 유기 용매에 녹인 형태로 정맥 주사에 사용된다. 높은 함량의 부형제는 전신 과민증, 심혈관 부작용 등을 유발할 수 있어서, 부형제 함량을 줄이는 나노결정 제제가 연구되고 있다. 본 연구의 도세탁셀 나노입자 제조에서 입자 크기와 크기 분포를 기준으로 최적화된 공정은 상분리와 고압균질화를 결합한 형태였다. 도세탁셀을 1-tetradecanol 매트릭스에 poly(vinyl pyrrolidone)과 같이 녹인 후 냉각 상분리하여 무정형 나노 전구체를 얻었으며, 전구체를 고압균질화를 통해 수분산하여 약 200 nm의 나노결정을 제조하였다. 암세포 cluster가 도입된 chicken chorioallantoic membrane을 활용하여 도세탁셀 나노입자를 시험한 결과, 주변 정상 조직에 대한 확연한 손상을 보이지 않으면서 암 조직 크기의 유의미한 감소가 관측되었다.


Keywords: docetaxel, nanocrystal, amorphous precursor, poly(vinyl pyrrolidone), enhanced permeability and retention.

  • Polymer(Korea) 폴리머
  • Frequency : Bimonthly(odd)
    ISSN 0379-153X(Print)
    ISSN 2234-8077(Online)
    Abbr. Polym. Korea
  • 2020 Impact Factor : 0.493
  • Indexed in SCIE

This Article

  • 2022; 46(2): 275-280

    Published online Mar 25, 2022

  • 10.7317/pk.2022.46.2.275
  • Received on Dec 21, 2021
  • Revised on Dec 21, 2021
  • Accepted on Jan 7, 2022

Correspondence to

  • Jae Hyun Jeong , and Il Won Kim
  • Department of Chemical Engineering, Soongsil University, Seoul 06978, Korea

  • E-mail: nfejjh@ssu.ac.kr, iwkim@ssu.ac.kr