Article
  • Donepezil-loaded Poly(D,L-lactic acid) Microspheres for Potent and Sustained Drug Release in the Treatment of Alzheimer’s Disease

  • Eunyoung Seol*, **, Kwonhyeok Yoon*, Heeyong Lee*, Seong-Jun Jo*****, Jong II Park****,† , Sung-Joo Hwang***,† , and Cheong-Weon Cho**,†

  • *G2GBIO, Inc., 1646 Yuseong-daero, Science Park #302, Yuseong-gu, Daejeon 34054, Korea
    **College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-Gu, Daejeon 34134, Korea
    ***Yonsei Institute of Pharmaceutical Sciences & College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-Gu, Incheon 21983, Korea
    ****Department of Bio Nanomaterials, Bio Campus of Korea Polytechnics, #48, Dongan-ro 112, Ganggeong-up, Nonsan, Chungnam 32943, Korea
    *****College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon 14662, Korea

  • 알츠하이머 치료를 위한 PLA 서방형 미립구 제형 개발

  • 설은영*, ** ·윤권혁* ·이희용* ·조성준***** · 박종일****,† · 황성주***,† · 조정원**,†

  • *㈜지투지바이오, **충남대학교 약학과, ***연세대학교 약학과 ****한국폴리텍대학 바이오나노소재과, *****가톨릭대학교 약학과

  • 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

Alzheimer’s disease is a progressive neurodegenerative disease associated with memory deficit and cognitive decline. Herein, a new formulation of donepezil-loaded microspheres of uniform particle size was investigated. Donepezil-loaded microspheres were successfully prepared using a cross-flow membrane emulsification technology. The size analysis showed that the average diameter of the microspheres was 58-83 μm, indicating a narrow size distribution with a span value of less than 0.71. Scanning electron microscopy showed that the microspheres had a spherical shape. The loading efficiency of donepezil in the poly(D,L-lactic acid) (PLA) microspheres was 61.8±3.7% (w/w). Donepezil-loaded microspheres prepared using PLA (DM-L3) presented a more sustained release efficacy than poly(lactic-co-glycolic acid) (PLGA) microspheres in an in vitro accelerated release test and single-dose subcutaneous pharmacokinetic test in rats. The concentration-time profile analyzed using the non-parametric superposition method showed that the DM-L3 microspheres could achieve a sustained release of the drug for 1 month.


알츠하이머병은 기억력 결핍 및 인지 저하가 수반되는 진행성 신경 퇴행성 질환이다. 본 연구에서는 도네페질(donepezil)이 함유된 균일한 입자크기를 갖는 신규한 미립구 제형에 대하여 연구하였다. 도네페질이 함유된 미립구는 막유화 기술을 이용하여 제조하였으며, 평균 직경은 58-83 μm, 스팬값은 0.71 미만으로 입도가 균일하였고, 전자현미경 관찰결과 입자가 구형으로 제조되었음을 확인하였다. Poly(D,L-lactic acid)(PLA) 미립구에서 도네페질의 봉입 효율이 61.8±3.7%(w/w)이었고, 가속 방출 시험 및 쥐의 단일 용량 피하 약동학 시험에서 poly(lactic-co-glycolic acid)(PLGA)으로 제조된 미립구보다 더 오랫동안 방출이 지속되는 것을 확인할 수 있었다. 비모수 중첩법을 사용하여 분석한 농도-시간 프로파일은 PLA를 이용하여 제조된 미립구인 DM-L3가 1개월 동안 체내에서 약물이 지속적으로 방출될 수 있음을 확인하였다.


Keywords: donepezil, Alzheimer's disease, microsphere, poly(D,L-lactic acid).

  • Polymer(Korea) 폴리머
  • Frequency : Bimonthly(odd)
    ISSN 0379-153X(Print)
    ISSN 2234-8077(Online)
    Abbr. Polym. Korea
  • 2022 Impact Factor : 0.4
  • Indexed in SCIE

This Article

  • 2022; 46(2): 238-245

    Published online Mar 25, 2022

  • 10.7317/pk.2022.46.2.238
  • Received on Nov 21, 2021
  • Revised on Jan 6, 2022
  • Accepted on Feb 8, 2022

Correspondence to

  • Jong II Park**** , Sung-Joo Hwang*** , and Cheong-Weon Cho**

  • **College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-Gu, Daejeon 34134, Korea
    ***Yonsei Institute of Pharmaceutical Sciences & College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-Gu, Incheon 21983, Korea
    ****Department of Bio Nanomaterials, Bio Campus of Korea Polytechnics, #48, Dongan-ro 112, Ganggeong-up, Nonsan, Chungnam 32943, Korea

  • E-mail: jipark@kopo.ac.kr, sjh11@yonsei.ac.kr, chocw@cnu.ac.kr