Mannose Receptors of Alveolar Macrophages as a Target for the Addressed Delivery of Medicines to the Lungs

• Published in: Russian journal of bioorganic chemistry 2022-02, Vol.48 (1), p.46-75
• Main Authors: Zlotnikov, I. D., Kudryashova, E. V.
• Format: Article
• Language: English
• Subjects: Arrays; Binding; Bioavailability; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Carbohydrates; Complex formation; Concanavalin A; Flow cytometry; Fluorescence; Infrared spectroscopy; Lectins; Life Sciences; Ligands; Macrophages; Mannose; Mathematical models; Oligosaccharides; Organic Chemistry; Parameters; Proteins; Receptors; Review Article; Screening; X ray analysis
• ISSN: 1068-1620; 1608-330X
• DOI: 10.1134/S1068162022010150

— This review was devoted to an investigation of the structure, properties, and functions of the mannose receptors of the alveolar macrophages which were promising targets for the creation of systems of the addressed delivery of medicines for treatment of diseases of the upper airways. In the first section, we discussed a search for an optimal strategy of studies of the ligand-receptor interactions and determination of the ligand specificity to the macrophage mannose receptors with the aim of improving the efficiency and organ bioavailability of drugs. The model proteins for a simulation of the ligand–protein interactions in the in vitro systems were reviewed. The use of concanavalin A as a model mannose-specific lectin allowed a determination of the binding parameters for ligands of different structure, a wide screening of the ligand array, and studies of the contribution of steric factors during the ligand binding. The latter was difficult in the case of such a complex target as the mannose receptor of the alveolar macrophages (CD206). This receptor is inaccessible, and adequate screening in vitro was technically difficult for them. In the second section, we described methods for determining the binding parameters of the carbohydrate-containing ligands to receptors and model lectins: IR spectroscopy, fluorescent methods, affinity chromatography, confocal microscopy, flow cytometry, X-ray analysis, and calorimetry. A large array of quantitative parameters of the complex formation of the oligosaccharide ligands with concanavalin A was analyzed. Selection of the optimal structure of the ligand by varying the density and the number of the mannose-containing ligands, and the spacer length, is considered as a basis for creation of the addressed delivery systems. The practical application of the described approaches to the creation and trials of the addressed delivery of the bioactive substances in the in vivo systems is discussed in the third section of this review.