임지홍 (건국대학교)

한빛사논문

조회164

건국대학교

CV File 100 kb

J. Control. Release, Jul 04 2024, S0168-3659(24)00439-5 | https://doi.org/10.1016/j.jconrel.2024.07.008 A novel chemically engineered multifunctional statin conjugate as self-assembled nanoparticles inhibiting bile acid transporters

Kyeong-Ju Lee ^a,1, Yoon-Mi Lee^c,1, Seong-Bin Yang ^a, Jun-Hyuck Lee ^a, Ha Rin Kim ^b, Ji-Hong Lim ^a,c, Jooho Park ^a,c

^aBK21 Program, Department of Applied Life Science, Konkuk University, Chungju 27478, Republic of Korea

^bSchool of Medicine, Stanford University, Stanford, CA 94305, United States

^cDepartment of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, Chungju 27478, Republic of Korea

¹These authors contributed equally to this work

Corresponding authors : Ji-Hong Lim, Jooho Park

Abstract

Statins are widely used to treat hyperlipidemia; however, their mechanism-inhibiting cholesterol production without promoting its utilization-causes problems, such as inducing diabetes. In our research, we develop, for the first time, a chemically engineered statin conjugate that not only inhibits cholesterol production but also enhances its consumption through its multifunctional properties. The novel rosuvastatin (RO) and ursodeoxycholic acid (UDCA) conjugate (ROUA) is designed to bind to and inhibit the core of the apical sodium-dependent bile acid transporter (ASBT), effectively blocking ASBT's function in the small intestine, maintaining the effect of rosuvastatin. Consequently, ROUA not only preserves the cholesterol-lowering function of statins but also prevents the reabsorption of bile acids, thereby increasing cholesterol consumption. Additionally, ROUA's ability to self-assemble into nanoparticles in saline-attributable to its multiple hydroxyl groups and hydrophobic nature-suggests its potential for a prolonged presence in the body. The oral administration of ROUA nanoparticles in animal models using a high-fat or high-fat/high-fructose diet shows remarkable therapeutic efficacy in fatty liver, with low systemic toxicity. This innovative self-assembling multifunctional molecule design approach, which boosts a variety of therapeutic effects while minimizing toxicity, offers a significant contribution to the advancement of drug development.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-16)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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