Pharmaceutics
Mannose-Functionalized Polymeric Micelles Target CD206-Expressing Macrophages Within Human Tuberculosis Granulomas and Improve Isoniazid Delivery
By Martinena CB, Ortellado FG, Vitti AD and 9 others.
Abstract
Background
Latent tuberculosis infection (LTBI) remains a global health challenge, in part due to the ability of Mycobacterium tuberculosis (Mtb) to persist within granulomatous lesions where drug exposure may be limited. Because granulomas are heterogeneous structures composed of different macrophage populations, targeting disease-relevant intracellular niches may improve antimicrobial treatment. Here, we developed mannose-functionalized polymeric micelles loaded with isoniazid (INH) to target mannose receptor (CD206)-expressing macrophages within a human tuberculosis granuloma model.
Methods
Mannose-functionalized Soluplus® micelles loaded with INH (ManPM-INH) and non-functionalized micelles (PM-INH) were characterized for particle size, polydispersity, and colloidal stability. Antimycobacterial activity against MtbH37Rv was evaluated by CFU assays. A human peripheral blood mononuclear cell (PBMC) three-dimensional in vitro granuloma model was used to assess micelle accumulation and antimycobacterial activity. Cellular uptake was evaluated in M0, M1, and M2 macrophages using rhodamine-labeled micelles. CD206-associated and clathrin-mediated uptake were investigated using D-mannose and chlorpromazine, respectively.