The role of mycobacterial effiux pumps in drug-resistant tuberculosis has been widely reported. Recently, a new compound, named SS13, has been synthesized, and its activity as a potential effiux inhibitor has been demonstrated. In this work, the chemical–physical properties of the SS13 were investigated; furthermore, a formulative study aimed to develop a formulation suitable for oral administration was performed. SS13 shows nonintrinsic antitubercular activity, but it increases the antitubercular activity of all the tested drugs on several strains. SS13 is insoluble in different simulated gastrointestinal media; thus, its oral absorption could be limited. Solid lipid nanoparticles (SLNs) were, therefore, developed by using two different lipids, Witepsol and/or Gelucire. Nanoparticles, having a particle size (range of 200–450 nm with regards to the formulation composition) suitable for intestinal absorption, are able to load SS13 and to improve its permeation through the intestinal mucosa compared to the pure compound. The cytotoxicity is influenced by the concentration of nanoparticles administered. These promising results support the potential application of these nanocarriers for increasing the oral permeation of SS13 in multidrug-resistant tuberculosis management. © 2020 by the authors.

Solid Lipid Nanoparticles as Formulative Strategy to Increase Oral Permeation of a Molecule Active in Multidrug-Resistant Tuberculosis Management / Obinu, Antonella; Porcu, Elena Piera; Piras, Sandra; Ibba, Roberta; Carta, Antonio; Molicotti, Paola; Migheli, Rossana; Dalpiaz, Alessandro; Ferraro, Luca; Rassu, Giovanna; Gavini, Elisabetta; Giunchedi, Paolo. - In: PHARMACEUTICS. - ISSN 1999-4923. - 12:12(2020), p. 1132. [10.3390/pharmaceutics12121132]

Solid Lipid Nanoparticles as Formulative Strategy to Increase Oral Permeation of a Molecule Active in Multidrug-Resistant Tuberculosis Management

Obinu, Antonella;Porcu, Elena Piera;Piras, Sandra;Ibba, Roberta;Carta, Antonio;Molicotti, Paola;Migheli, Rossana;Rassu, Giovanna;Gavini, Elisabetta
;
Giunchedi, Paolo
2020

Abstract

The role of mycobacterial effiux pumps in drug-resistant tuberculosis has been widely reported. Recently, a new compound, named SS13, has been synthesized, and its activity as a potential effiux inhibitor has been demonstrated. In this work, the chemical–physical properties of the SS13 were investigated; furthermore, a formulative study aimed to develop a formulation suitable for oral administration was performed. SS13 shows nonintrinsic antitubercular activity, but it increases the antitubercular activity of all the tested drugs on several strains. SS13 is insoluble in different simulated gastrointestinal media; thus, its oral absorption could be limited. Solid lipid nanoparticles (SLNs) were, therefore, developed by using two different lipids, Witepsol and/or Gelucire. Nanoparticles, having a particle size (range of 200–450 nm with regards to the formulation composition) suitable for intestinal absorption, are able to load SS13 and to improve its permeation through the intestinal mucosa compared to the pure compound. The cytotoxicity is influenced by the concentration of nanoparticles administered. These promising results support the potential application of these nanocarriers for increasing the oral permeation of SS13 in multidrug-resistant tuberculosis management. © 2020 by the authors.
Solid Lipid Nanoparticles as Formulative Strategy to Increase Oral Permeation of a Molecule Active in Multidrug-Resistant Tuberculosis Management / Obinu, Antonella; Porcu, Elena Piera; Piras, Sandra; Ibba, Roberta; Carta, Antonio; Molicotti, Paola; Migheli, Rossana; Dalpiaz, Alessandro; Ferraro, Luca; Rassu, Giovanna; Gavini, Elisabetta; Giunchedi, Paolo. - In: PHARMACEUTICS. - ISSN 1999-4923. - 12:12(2020), p. 1132. [10.3390/pharmaceutics12121132]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11388/239913
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