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
설은영*, ** ·윤권혁* ·이희용* ·조성준***** · 박종일****,† · 황성주***,† · 조정원**,†
*㈜지투지바이오, **충남대학교 약학과, ***연세대학교 약학과 ****한국폴리텍대학 바이오나노소재과, *****가톨릭대학교 약학과
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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).
2022; 46(2): 238-245
Published online Mar 25, 2022
**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