Surface engineering of Solid Lipid Nanoparticle assemblies by methyl α-d-mannopyranoside for the active targeting to macrophages in anti-tuberculosis inhalation therapy
| Autor: | Francesca Buttini, Eleonora Maretti, Eliana Leo, Maria Antonietta Croce, Valentina Iannuccelli, Cecilia Rustichelli, Luca Costantino, Eleonora Truzzi |
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| Rok vydání: | 2017 |
| Předmět: |
Respiratory Therapy
Macrophage uptake media_common.quotation_subject Pharmaceutical Science Mannose 02 engineering and technology Methylmannosides 030226 pharmacology & pharmacy Cell Line 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Drug Delivery Systems Phagocytosis Solid lipid nanoparticle Administration Inhalation Macrophage Animals Tuberculosis Internalization Cytotoxicity media_common Solid Lipid Nanoparticle assemblies Inhalation Surface mannosylation Macrophages 021001 nanoscience & nanotechnology Lipids chemistry Biochemistry Mannosylation Tripalmitin Alveolar macrophage Nanoparticles 0210 nano-technology |
| Zdroj: | International journal of pharmaceutics. 528(1-2) |
| ISSN: | 1873-3476 |
| Popis: | This study describes the development of new mannosylated Solid Lipid Nanoparticle assemblies (SLNas) delivering rifampicin for an inhaled treatment of tuberculosis. SLNas were surface engineered with mannose residues to recognize mannose receptors located on infected alveolar macrophages and facilitate cell internalization. Two sets of SLNas were produced by the melt emulsifying technique using biocompatible lipid components, i.e. cholesteryl myristate combined with palmitic acid (PA set) or tripalmitin (TP set), in the presence of the targeting moiety, methyl α-d-mannopyranoside. Mannosylated SLNas were examined for their physical properties, drug payloads and release, as well as respirability in terms of emitted dose and respirable fraction determined by Next Generation Impactor. The most appropriate formulations were assessed for mannosylation using FTIR, XPS, SEM coupled with EDX analysis, and wettability assay, in comparison with the respective non-functionalized SLNas. Besides, cytotoxicity and cell internalization ability were established on J774 murine macrophage cell line. Mannosylated SLNas exhibited physical properties suitable for alveolar macrophage passive targeting, adequate rifampicin payloads (10-15%), and feasible drug maintenance within SLNas along the respiratory tract before macrophage internalization. Despite respirability impaired by powder cohesiveness, surface mannosylation provided quicker macrophage phagocytosis, giving evidence of an active targeting promotion. |
| Databáze: | OpenAIRE |
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