pharmjournalРазработка и регистрация лекарственных средствDrug development & registration2305-20662658-5049LLC «CPHA»10.33380/2305-2066-2022-11-3-97-112pharmjournal-1290Research ArticleФАРМАЦЕВТИЧЕСКАЯ ТЕХНОЛОГИЯPHARMACEUTICAL TECHNOLOGYКонструкция иммунолипосом (обзор)The Construction of Immunoliposomes (Review)ДмитриеваМ. В.DmitrievaM. V.

115478, г. Москва, Каширское шоссе, д. 24

24, Kashirskoe highway, Moscow, 115478

dmitrieva.m@ronc.ruЯрошИ. В.YaroshI. V.

119421, г. Москва, Ленинский пр-т, д. 111, к. 1

111/1, Leninsky pr-t, Moscow, 119421

СанароваЕ. В.SanarovaE. V.

115478, г. Москва, Каширское шоссе, д. 24

24, Kashirskoe highway, Moscow, 115478

ЛанцоваА. В.LantsovaA. V.

115478, г. Москва, Каширское шоссе, д. 24

24, Kashirskoe highway, Moscow, 115478

ОрловаО. Л.OrlovaO. L.

115478, г. Москва, Каширское шоссе, д. 24

24, Kashirskoe highway, Moscow, 115478

ФГБУ «Национальный медицинский исследовательский центр онкологии имени Н. Н. Блохина» Минздрава России (НМИЦ онкологии им. Н. Н. Блохина)РоссияFSBI "National Medical Research Center of Oncology. N. N. Blokhin"Russian FederationАО «Р-Фарм»РоссияJSC "R-Pharm"Russian Federation20223008202211397112Copyright © Дмитриева М.В., Ярош И.В., Санарова Е.В., Ланцова А.В., Орлова О.Л., 20222022Дмитриева М.В., Ярош И.В., Санарова Е.В., Ланцова А.В., Орлова О.Л.Dmitrieva M.V., Yarosh I.V., Sanarova E.V., Lantsova A.V., Orlova O.L.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmjournal.ru/jour/article/view/1290Введение

Введение. Благодаря открытию антител (АТ), нацеливающей молекулы с высокой специфичностью к лиганду, концепция «волшебная пуля» была успешно реализована с различными иммуноконъюгированными лекарственными средствами (ЛС). С 1980 г. для повышения специфичности и эффективности лекарственной терапии стали широко исследоваться конъюгаты АТ с липосомами, т. е. иммунолипосомы (ИЛ). Данный обзор посвящен характеристике основных структурных единиц ИЛ на основе анализа данных оригинальных и обзорных статей по теме исследования из баз PubMed, ResearchGate и КиберЛенинка.

Текст

Текст. ИЛ представляют собой липосомы, к которым обычно посредством специального линкера прикреплены АТ, их фрагменты или иные лиганды. ИЛ используются для доставки противоопухолевых, сердечно-сосудистых, противовирусных, противопротозойных ЛС, генетического материала, визуализирующих молекул и др. ИЛ могут быть получены из различных фосфолипидов как природного, так и синтетического происхождения, заряженных или нейтральных. Наиболее широко используемыми фосфолипидами в иммунолипосомальной конструкции являются фосфатидилхолины. Для повышения механической устойчивости бислоя в липидную композицию вводят стерины. Для селективной доставки липосом нацеливающие лиганды должны быть прикреплены к наноносителю через спейсерное плечо ПЭГ. Для этой цели используют несколько типов функционализированных концевыми группами липополимеров обычно общей формулы Х-PEG-LI, где Х представляет собой фрагмент, содержащий реакционноспособную функциональную группу, − малеимид, биотин, цианур, амин и др. Эти липидные ПЭГ-конъюгаты демонстрируют превосходные амфифильные свойства и предлагают превосходные преимущества для модификации, формулирования и доставки различных ЛС. Используемое АТ должно усиливать накопление липосомального ЛС в целевых областях с минимальной перекрестной реактивностью со здоровыми тканями. При приготовлении ИЛ используют готовые лекарственные препараты на основе моноклональных АТ, например трастузумаб, цетуксимаб, панитумумаб, бевацизумаб, также применяют коммерческие АТ, предназначенные для исследовательских целей, и синтезированные в лабораторных условиях АТ и их фрагменты. АТ могут быть прикреплены к липосомам двумя основными способами: прямой ковалентной конъюгации и постинсерционным методом.

Заключение

Заключение. Результаты проведенного исследования позволили обобщить многообразие литературных данных о составе ИЛ и возможности использования вспомогательных компонентов для достижения поставленной цели при разработке препарата.

Introduction

Introduction. Due to the discovery of antibodies (Ab) targeting molecule with high specificity to the ligand, the "magic bullet" concept has been successfully implemented with various immunoconjugated drugs. Since 1980, Ab conjugates with liposomes, i.e., immunoliposomes (ILs), have been widely investigated to improve the specificity and efficacy of drug therapy. This review is devoted to the characteristic of the basic structural units of ILs on the basis of data analysis of original and review articles on the topic from PubMed, ResearchGate and CyberLeninck databases.

Text

Text. ILs are liposomes to which Ab, their fragments or other ligands are usually attached by a special linker. ILs are used to deliver antitumor, cardiovascular, antiviral, antiprotozoal drugs, genetic material, imaging molecules, etc. ILs can be derived from various phospholipids of both natural and synthetic origin, charged or neutral. The most widely used phospholipids in immunoliposomal construction are phosphatidylcholines. To increase the mechanical stability of the bilayer, sterols are introduced into the lipid composition. For selective liposome delivery, targeting ligands must be attached to the nanocarrier via the spacer arm of the PEG. Several types of end-group functionalized lipopolymers are used for this purpose, usually of the general formula X-PEG-LI, where X represents a fragment containing a reactive functional group − maleimide, biotin, cyanur, amine, etc. These lipid PEG-conjugates exhibit excellent amphiphilic properties and offer excellent advantages for the modification, formulation, and delivery of various drugs. The Ab used should enhance the accumulation of the liposomal drug in the target areas with minimal cross-reactivity with healthy tissues. Ready-made drugs based on monoclonal Ab, such as trastuzumab, cetuximab, panitumumumab, bevacizumab; commercial Ab intended for research purposes, and laboratory synthesized Ab and their fragments are used in the preparation of ILs. Ab can be attached to liposomes by two main methods: direct covalent conjugation and postinsertion.

Conclusion

Conclusion. The results of this study allowed us to summarize the variety of literature data on the composition of ILs and the possibility of using auxiliary components to achieve the goal in the development of the drug.

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The authors declare that there are no conflicts of interest present.