Ion-powered drugs
Ionic and covalent drug delivery
ChemPort.Ru based on the materials of the IOH RAS press release, Ionic and covalent drug delivery
Scientists from the N.D. Zelinsky Institute of Organic Chemistry have developed the concept of API-IL (active pharmaceutical ingredient – ionic liquid, API – active pharmaceutical ingredient; IL – ionic liquid) to achieve structural diversity in pharmaceuticals, as well as the creation of dual-acting drugs.
Article by Egorova et al. Cytotoxic Activity of Salicylic Acid-Containing Drug Models with Ionic and Covalent Binding is published in the journal ACS Medicinal Chemistry Letters – VM.
The active pharmaceutical ingredients (API1 and API2) can be bound to an ionic liquid by an ionic or covalent bond. The ability of an ionic liquid to "tune" allows you to vary its properties at the molecular level. The results of the study open up new possibilities for drug design using ionic and covalent molecular interactions.
The human body consists of many simple and complex molecules, and all the main processes in a living organism occur in aqueous solutions. Thus, for the effective operation of the drug, it is necessary that it dissolves in water.
One of the problems of using solids as medicines is their polymorphism, that is, the ability to form various crystal structures (polymorphic modifications). Polymorphs can vary in their properties (such as biological activity), and their formation is difficult to control. The problem of crystal polymorphism can be solved by using drugs in liquid form, since the use of solutions makes therapy more reliable and predictable. It is not surprising that methods of dissolving existing active pharmaceutical ingredients are being actively investigated.
An effective solution to this problem can be achieved with the help of substances with an ionic structure. It is well known that the conversion of a poorly soluble substance into salt can significantly improve its solubility. A group of scientists led by V.P. Ananikov showed that ionic liquids are excellent "intermediaries" for the transformation of organic molecules into salt structures. In the work of Russian scientists, three methods of introducing active pharmaceutical ingredients into ionic liquids were studied: I) as an anion or cation (ionic bond); ii) using a covalent bond; iii) with simultaneous use of ionic and covalent bonds.
The proposed platform for drug development has the following advantages: 1. Adjustable hydrophobicity/lipophilicity to adjust the ability to penetrate cell membranes and other biological barriers. 2. An ionic "core" that allows you to control the strength of the ionic bond. Ionic liquids can be "customized" and can be easily optimized to work with various pharmaceutical ingredients. 3. Variable linker for regulating the distance between the ionic "core" and the active ingredient. This linker may contain an enzymatic cleavage site for the targeted release of an active pharmaceutical ingredient.
The API-IL concept allows combining different pharmaceutical ingredients in a single molecule. Scientists used salicylic acid (a well-known anti-inflammatory drug) as a model drug.
Salicylic acid molecules were introduced into ionic liquids, after which the solubility and biological activity with respect to human fibroblasts and colorectal adenocarcinoma cells were investigated. Indeed, salicylic acid retained its activity in the composition of the ionic liquid, and the ionic liquid based on it showed higher solubility in water compared to pure salicylic acid. The study confirms the advantages of using the API-IL concept in pharmaceuticals.
It is especially important to note the availability and variety of possible combinations of molecules. A very promising direction is the production of "double-acting" ion-liquid preparations carrying two different active pharmaceutical ingredients. This approach will allow us to develop comprehensive treatment methods aimed at eliminating several causes of pathologies at once.
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12.10.2015