1. Academic Validation
  2. Surface engineering of Solid Lipid Nanoparticle assemblies by methyl α-d-mannopyranoside for the active targeting to macrophages in anti-tuberculosis inhalation therapy

Surface engineering of Solid Lipid Nanoparticle assemblies by methyl α-d-mannopyranoside for the active targeting to macrophages in anti-tuberculosis inhalation therapy

  • Int J Pharm. 2017 Aug 7;528(1-2):440-451. doi: 10.1016/j.ijpharm.2017.06.045.
Eleonora Maretti 1 Luca Costantino 1 Cecilia Rustichelli 1 Eliana Leo 1 Maria Antonietta Croce 1 Francesca Buttini 2 Eleonora Truzzi 1 Valentina Iannuccelli 3
Affiliations

Affiliations

  • 1 Department of Life Sciences, University of Modena and Reggio Emilia, via G. Campi 103, 41125 Modena, Italy.
  • 2 Department of Food and Drug Science, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy.
  • 3 Department of Life Sciences, University of Modena and Reggio Emilia, via G. Campi 103, 41125 Modena, Italy. Electronic address: [email protected].
Abstract

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.

Keywords

Cholesteryl myristate (PubChem CID: 313252); Inhalation; Macrophage uptake; Methyl α-d-mannopyranoside (PubChem CID: 101798); Palmitic acid (PubChem CID: 985); Rifampicin (PubChem CID: 5381226); Sodium taurocholate (PubChem CID: 23666345); Solid lipid nanoparticle assemblies; Surface mannosylation; Tripalmitin (PubChem CID: 11147); Tuberculosis.

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