Triglycerides/Hypertriglyceridemia
Charles Theisler in Adjuvant Medical Care, 2023
Triglycerides are a type of lipid, or fat, found in the blood. The body converts extra calories into triglycerides and stores them in fat cells. Untreated or uncontrolled high blood triglyceride levels increase the risk of serious complications such as coronary heart disease, cardiovascular events, and stroke. Very high blood triglycerides can also increase the risk of acute pancreatitis, which is inflammation of the pancreas that causes severe pain in the abdomen.1 High triglycerides can be a sign of other comorbid conditions that increase the risk of heart disease and stroke, such as obesity and metabolic syndrome (also known as insulin resistance syndrome) which is a cluster of conditions that includes too much fat around the waist, high blood pressure, high triglycerides, high blood sugar, and abnormally low high-density lipoprotein (HDL) cholesterol levels).2
Nanomaterials in Chemotherapy
D. Sakthi Kumar, Aswathy Ravindran Girija in Bionanotechnology in Cancer, 2023
Lipids are highly hydrophobic in nature, hence insoluble in water, and typically consist of saturated or unsaturated hydrocarbon motifs often connected to glycerol. For instance, a triglyceride is composed of three fatty acids linked via ester bonds to glycerol. Many of the lipids are isolated from their biological origin, which then purified via chromatographic separations. Progresses in the field of lipid synthesis with high purity diversified the scope of using lipid as a ‘solubilizer’ in cosmetics and foods, and as a ‘building block’ for making nanoscale materials. Phospholipids are a class of lipids with amphiphilic characteristics due to the presence of both hydrophobic fatty acid chain and a hydrophilic phosphate group. In an aqueous environment, phospholipid tends to form a bilayer architecture as in the case of the biological cell membrane. Since the phosphate part of the phospholipids can be easily functionalized with organic molecules, such as choline, a wide variety of modified phospholipids have been developed that form interesting nanostructures. Liposome is a representative example formed by the self-assembly of phospholipid derivatives, such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol, which have been found applications in various fields including DDSs.
The Scientific Basis of Medicine
John S. Axford, Chris A. O'Callaghan in Medicine for Finals and Beyond, 2023
The structural units of lipids are fatty acids, containing long chains of 4–24 carbon atoms joined to a carboxylic acid group (Figure 2.4). Fatty acids may be saturated or non-saturated depending on the presence of double bonds within their hydrocarbon tail. Polyunsaturated fatty acids contain multiple double bonds. One of the most important in vivo functions performed by lipids is the formation of cellular membranes. Phospholipids contain a hydrophilic phosphate group, linked by glycerol to a hydrophobic fatty acid tail. The amphipathic nature of phospholipids allows them to form a sealed membrane bilayer in aqueous solution. Another physiologically important group of lipids are the cholesterol derivatives (steroids). These molecules contain four hydrocarbon rings, one of which carries a hydroxyl group which gives the molecule an amphipathic nature.
A novel micellar carrier to reverse multidrug resistance of tumours: TPGS derivatives with end-grafted cholesterol
Published in Journal of Drug Targeting, 2023
Zhaowei Qi, Jia Shi, Yanzhi Song, Yihui Deng
Hydrophobic modification is the most effective way to reduce the CMC value. Cholesterol is a lipid widely present in animals, and it is indispensable for cellular functions. Cancer cells require cholesterol for rapid proliferation and accumulate high amounts of cholesterol, which either rely on upregulated cholesterol biosynthesis or enhance the uptake of cholesterol [17]. Clinical trials have also shown that cancer cells, such as prostate, breast, liver, gastric and oesophageal cancers have high cholesterol content [18–20]. Zhang et al. [21] showed that liposomes containing high cholesterol concentrations had higher tumour tissue distribution. Therefore, cholesterol acts as a target ligand. Unexpectedly, cholesterol has a high affinity for the centre of the polycyclic structure of paclitaxel and can form a stable stereo complex. Lee et al. [22] used the cholesterol-containing amphiphilic carrier material poly[(N-methyldietheneamine sebacate)-co-[(cholesteryl oxocarbonylamido ethyl) methyl bis(ethylene) ammonium bromide] sebacate (P(MDS-CO-CES) to prepare drug-loaded micelles with a drug-loading capacity of 14% and an encapsulation efficiency of 92% through self-assembly alone.
Reality check: lipid-oligonucleotide conjugates for therapeutic applications
Published in Expert Opinion on Drug Discovery, 2023
Robert A Goodnow
Lipids are often defined as fairly large bio-molecules that are soluble in nonpolar solvents, the sorts of solvents that are used to isolate such molecules from cellular membrane sources. Lipids are usually thought of as ‘natural substances,’ or as opposed to small molecules, usually discovered by medicinal chemistry, which are often made entirely from ‘unnatural’ or synthetic substances. This differentiation is based on the presumption that natural lipids are safe and nontoxic substances, whereas small molecules can only be considered safe as their dosing regimens proves them to be. Of course, these presumptions are entirely speculative. The safety of any substance, whether natural or synthetic, is a question of dose. In any case, conjugation lipophiles often are selected from the following: lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, α-linoleic acid, γ-linoleic acid, cis-DHA acid, α-tocopherol acid, and cholesterol. It is important to note that by the chemistry of covalent attachment, these substances become different molecular entities with, though perhaps related, certainly different properties; in other words, one should resist arbitrary and potentially inaccurate modulization or compartmentalization of the molecular entities and their functions that comprise lipidated oligo conjugates.
Functional ligands for improving anticancer drug therapy: current status and applications to drug delivery systems
Published in Drug Delivery, 2022
Rajiv Bajracharya, Jae Geun Song, Basavaraj Rudragouda Patil, Sang Hoon Lee, Hye-Mi Noh, Da-Hyun Kim, Gyu-Lin Kim, Soo-Hwa Seo, Ji-Won Park, Seong Hoon Jeong, Chang Hoon Lee, Hyo-Kyung Han
Cholesterol is a neutral lipid that plays a vital role in the maintenance of the integrity of biological membranes and serves as a precursor in the synthesis of many endocrine mediators (Tong, 2011). Cholesterol is biocompatible, biodegradable, highly permeable, readily available, and inexpensive (Ruwizhi & Aderibigbe, 2020). Its functional groups are also easily derivatized. The incorporation of cholesterol to drugs or drug carriers can enhance their biological activities, stability, or cellular uptake (Ruwizhi & Aderibigbe, 2020; Tedesco et al., 2021). Accordingly, chemical modification of drug carriers with cholesterol has been attempted in various delivery systems, including nanoparticles, micelles, niosomes, and liposomal formulations (Ruwizhi & Aderibigbe, 2020). Cholesterol-modified carriers have the ability to incorporate both lipophilic and hydrophilic drugs with high drug loading efficiency and could enhance the intracellular uptake (Muddineti et al., 2018; Nakhaei et al., 2021). Muddineti et al. (2018) developed cholesterol-modified low molecular-weight chitosan for co-delivery of siRNA and curcumin to cancer cells. The cholesterol-modified chitosan micelles exhibited optimum physicochemical characteristics, dual drug loading capability, and enhanced intracellular drug uptake (Muddineti et al., 2018).