김소희 (아주대학교)

한빛사논문

조회204

김소희So Hee Kim

아주대학교

J. Control. Release, Jan 08 2024, 366 S0168-3659(23)00833-7 | https://doi.org/10.1016/j.jconrel.2023.12.049 Pre-mixing of omega-3 fatty acid-containing liposomes enhances the drug release rate and therapeutic efficacy of anticancer drugs loaded in liposomes

Eun-A Kim ^a,1, Hyeon Gyeom Choi ^b,1, Bao Loc Nguyen ^c, Su-Jin Oh ^a, Soo-Bin Lee ^a, Sung Hun Bae ^d, So Yeon Park ^e, Jong Oh Kim ^c, So Hee Kim ^b,d,e, Soo-Jeong Lim ^a

^aDepartment of Integrated Bioscience and Biotechnology, Sejong University, 209 Neungdong-ro, Gwangjin-gu, Seoul, Republic of Korea

^bCollege of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University, 206 Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea

^cCollege of Pharmacy, Yeungnam University, Gyongsan 38541, Republic of Korea

^dAI-Superconvergence KIURI Translational Research Center, Ajou University School of Medicine, Suwon 16499, Republic of Korea

^eDepartment of Biohealth Regulatory Science, Graduate School of Ajou University, 206 Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea

¹These authors contributed equally to this work.

Corresponding authors: So Hee Kim, Soo-Jeong Lim

Abstract

The therapeutic efficacy of anticancer drugs loaded in liposomes composed of rigid phosphatidylcholine (PC) is hindered by the limited release of these drugs at the tumor site, which in turn hampers delivery of the drug to its intracellular target. In an attempt to improve the therapeutic efficacy of liposomal anticancer drugs, we here explored the use of empty liposomes as "trigger" vehicles to induce drug release from drug-loaded liposomes through liposome-liposome interactions. Empty liposomes containing PC in which omega-3 fatty acids comprised both fatty acid strands (Omega-L) showed a triggering effect on drug release from doxorubicin (DOX)-loaded liposomes (Caelyx). The effectiveness of this triggered-release effect was dependent on the Omega-L composition as well as the mixing ratio of Omega-L to Caelyx. Cryo-TEM and differential calorimetry studies revealed that the Omega-L effect was associated with liposome-liposome interactions that led to loosened membrane packing and increased fluidity of Caelyx. In cultured cells, the intracellular/intranuclear DOX uptake and anticancer efficacy of Caelyx was greatly improved by Omega-L pre-mixing. Intravenous injection of rats with Caelyx, premixed with Omega-L, decreased the area under the plasma concentration-time curve from time zero to time infinity and increased clearance without significantly changing the mean residence time or terminal half-life of DOX compared with Caelyx alone. Ex vivo bioimaging showed that DOX fluorescence in tumors, but not in other organs, was significantly increased by Omega-L premixing. In the mouse xenograft model, premixing of Omega-L with Caelyx suppressed tumor growth 2.5-fold compared with Caelyx. Collectively, the data provide preliminary evidence that the Omega-L-triggered drug release that occurs before and after dosing, particularly at tumor site, improved the therapeutic efficacy of Caelyx. The simple approach described here could enhance the therapeutic value of Caelyx and other anticancer drug-loaded liposomes.

논문정보

형식Research article
게재일2024년 01월 (BRIC 등록일 2024-01-23)
연구진국내 연구진
분야

댓글 작성 로그인

CV 열람하기

연락처 보기