1. Introduction
ω-3 fatty acids, very-low-density lipoprotein cholesterol, gastrointestinal tract, hyperlipidemia
DISORDER, ADVERSE EFFECTS, HYPERLIPIDEMIA, HYPERLIPIDEMIA
Kwi-Man Kang and Sang-Won Jeon have equal Contribution as First Authors.Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are well known for their capacity to lower triglyceride levels, but the clinical effectiveness is hindered by limited bioavailability and patient adherence. To address this challenge, we introduce a novel liquid crystalline nanoparticle-based formulation, the innovative medicine and drug delivery (IMD)-Omega soft capsule (cap), designed to optimize the pharmacokinetics (PK) and safety of EPA and DHA. This randomized, open-label, crossover study engages a cohort of 24 healthy adult subjects, utilizing key PK parameters like CHyperlipidemia, a common worldwide disorder, is a condition characterized by abnormally high levels of low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), and triglycerides in the blood [In the age of modern medication, high-intensity statins are often recommended as a first-line treatment for hyperlipidemia in reducing LDL-C levels. These statins are potent cholesterol-lowering drugs that have demonstrated effectiveness in lowering LDL-C levels and reducing the risk of cardiovascular incidents [One promising therapeutic approach for managing hyperlipidemia involves the use of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are both long-chain ω-3 polyunsaturated fatty acids [The therapeutic potential of EPA and DHA has received significant attention, leading to the approval of several formulations by the U.S. Food and Drug Administration (FDA) as prescription drugs [Despite the well-proven efficacy of ethyl ester formulations, ω-3 fatty acids face significant challenges related to their bioavailability and absorption. When consumed in a fasting state, their bioavailability is relatively low, primarily due to their high lipophilicity, which influences their ability to reach the unstirred water layers of the gastrointestinal tract for absorption [A well-known commercial ω-3 ethyl ester product is the OmacorTo address these challenges and optimize the therapeutic potential of ω-3 fatty acids, ongoing research is actively looking for alternative delivery methods and formulations. Microencapsulation, emulsions, and nanoemulsions are some of the innovative approaches being investigated to enhance the stability and absorption of these essential fatty acids. These developments aim to improve patient acceptability and overall treatment results by increasing bioavailability, lowering the necessary dose, and decreasing adverse effects. In our previous study, we made significant progress in addressing the limitations of current commercial ω-3 acid ethyl ester products by developing a groundbreaking liquid crystalline nanoparticle-based formulation called the IMD-Omega soft capsule (IMD-Omega) [Given these encouraging results, our current study aims to explore deeper the pharmacokinetics (PK) and safety profiles of the IMD-Omega formulation of ω-3 fatty acids on a randomized, open-label, single-dose, crossover trial of IMD-Omega in healthy adults. We will conduct comprehensive evaluations and comparisons with the commercially available Omacor