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Drug Delivery and Translational Research

, Volume 9, Issue 1, pp 298–310 | Cite as

Newly synthesized surfactants for surface mannosylation of respirable SLN assemblies to target macrophages in tuberculosis therapy

  • Eleonora Maretti
  • Luca Costantino
  • Francesca Buttini
  • Cecilia Rustichelli
  • Eliana Leo
  • Eleonora Truzzi
  • Valentina IannuccelliEmail author
Original Article

Abstract

The present study reports about new solid lipid nanoparticle assemblies (SLNas) loaded with rifampicin (RIF) surface-decorated with novel mannose derivatives, designed for anti-tuberculosis (TB) inhaled therapy by dry powder inhaler (DPI). Mannose is considered a relevant ligand to achieve active drug targeting being mannose receptors (MR) overexpressed on membranes of infected alveolar macrophages (AM), which are the preferred site of Mycobacterium tuberculosis. Surface decoration of SLNas was obtained by means of newly synthesized functionalizing compounds used as surfactants in the preparation of carriers. SLNas were fully characterized in vitro determining size, morphology, drug loading, drug release, surface mannosylation, cytotoxicity, macrophage internalization extent and ability to bind MR, and intracellular RIF concentration. Moreover, the influence of these new surface functionalizing agents on SLNas aerodynamic performance was assessed by measuring particle respirability features using next generation impactor. SLNas exhibited suitable drug payload, in vitro release, and more efficient ability to enter macrophages (about 80%) compared to bare RIF (about 20%) and to non-functionalized SLNas (about 40%). The involvement of MR-specific binding has been demonstrated by saturating MR of J774 cells causing a decrease of RIF intracellular concentration of about 40%. Furthermore, it is noteworthy that the surface decoration of particles produced a poor cohesive powder with an adequate respirability (fine particle fraction ranging from about 30 to 50%). Therefore, the proposed SLNas may represent an encouraging opportunity in a perspective of an efficacious anti-TB inhaled therapy.

Keywords

Lipid nanoparticles Inhalation Mannose derivatives Macrophage targeting Tuberculosis Respirability 

Notes

Acknowledgments

This work was supported by FAR2017 from the University of Modena and Reggio Emilia. The authors thank Prof. Gilberto Coppi, Dr. Maria Antonietta Croce, Dr. Mauro Zapparoli, and Dr. Cinzia Restani for their excellent assistance. The authors would like to thank Plastiape Spa (Osnago, LC, Italy) and Capsugel (Morristown, New Jersey, USA) for kindly donating the RS01 dry powder inhalers and capsules, respectively.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

13346_2018_607_MOESM1_ESM.docx (2.5 mb)
ESM 1 (DOCX 2511 kb)

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Copyright information

© Controlled Release Society 2018

Authors and Affiliations

  1. 1.Department of Life SciencesUniversity of Modena and Reggio EmiliaModenaItaly
  2. 2.Food and Drug DepartmentUniversity of ParmaParmaItaly

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