1. Multicompartment vectors as novel drug delivery systems: selective activation of Tγδ lymphocytes after zoledronic acid delivery.
- Author
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Agrati C, Marianecci C, Sennato S, Carafa M, Bordoni V, Cimini E, Tempestilli M, Pucillo LP, Turchi F, Martini F, Borioni G, and Bordi F
- Subjects
- Bone Density Conservation Agents metabolism, Diphosphonates metabolism, Humans, Imidazoles metabolism, Leukocytes metabolism, Liposomes, Macrophages metabolism, Nanomedicine, Polylysine chemistry, Polylysine metabolism, Receptors, Antigen, T-Cell, gamma-delta metabolism, Zoledronic Acid, Bone Density Conservation Agents administration & dosage, Diphosphonates administration & dosage, Imidazoles administration & dosage, Lymphocyte Activation drug effects, T-Lymphocytes metabolism
- Abstract
Multicompartment nanoscopic carriers can be easily assembled by inducing the aggregation of anionic "hybrid" niosomes by means of cationic biocompatible polyelectrolytes. The resulting vesicle clusters, whose size and overall net charge can be easily controlled by varying the polyelectrolyte-to-particle charge ratio, show an interesting potential for multidrug delivery. In this article we provide strong evidence for their effective use in vitro as multicompartment vectors selectively directed toward monocyte/macrophage cells, showing that the monocyte/macrophage-mediated activation of Tγδ lymphocytes induced by zoledronic acid is enhanced by a factor 10(3) when the zoledronic acid is intracellularly delivered through these carriers. Furthermore, the multicompartment ɛ-polylysine niosome clusters, with their intrinsic selectivity toward macrophages, appear particularly suitable for implementing therapeutic strategies against chronically infected macrophages., From the Clinical Editor: ɛ-polylysine niosome clusters, with their intrinsic selectivity toward macrophages, offer the potential for multidrug delivery. The effectiveness of aminobisphosphonate zoledronate is demonstrated to enhance the recruitment of Tγδ lymphocytes by macrophages by 2 orders of magnitude, suggesting a new therapeutic strategy for addressing pathologies featuring chronically infected macrophages., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
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