Design of a nanostructured lipid carrier intended to improve the treatment of tuberculosis

Abstract

This work aimed to design, develop, and characterize a lipid nanocarrier system for the selective delivery of rifabutin (RFB) to alveolar macrophages. Lipid nanoparticles, specifically nanostructured lipid carriers (NLC), were synthetized by the high-shear homogenization and ultrasonication techniques. These nanoparticles were designed to exhibit both passive and active targeting strategies to be efficiently internalized by the alveolar macrophages, traffic to the acidified phagosomes and phagolysosomes, and release bactericidal concentrations of the antituberculosis drug intracellularly. NLC that could entrap RFB were prepared, characterized, and further functionalized with mannose. Particles’ diameter, zeta potential, morphology, drug% entrapping efficiency, and drug release kinetics were evaluated. The mannose coating process was confirmed by Fourier transform infrared. Further, the cytotoxicity of the formulations was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay in A549, Calu-3, and Raw 264.7 cells. The diameter of NLC formulations was found to be in the range of 175–213 nm, and drug entrapping efficiency was found to be above 80%. In addition, high storage stability for the formulations was expected since they maintained the initial characteristics for 6 months. Moreover, the drug release was pH-sensitive, with a faster drug release at acidic pH than at neutral pH. These results pose a strong argument that the developed nanocarrier can be explored as a promising carrier for safer and more efficient management of tuberculosis by exploiting the pulmonary route of administration.

Keywords:

• lipid nanoparticles
• mannose
• nanostructured lipid carriers
• rifabutin
• tuberculosis
• drug delivery systems

Supplementary materials

Table S1 Value of R² obtained from the release of RFB from the NLC-RFB lyophilized formulation for different models of mechanism of drug release

Table S2 Value of R² obtained from the release of RFB from the M-NLC-RFB lyophilized formulation for different models of mechanism of drug release

Acknowledgments

Alexandre Vieira thanks the CNPq, Ministry of Education of Brazil for the fellowship 246514/2012-4. Marina Pinheiro is thankful to Fundação para a Ciência e Tecnologia (FCT) for the Post-Doctorate Grant (SFRH/BPD/99124/2013). Additionally, this work was possible with financial support from FCT/MEC through National Funds and co-financed by FEDER, under the partnership agreement PT2020 - UID/MULTI/04378/2013 -POCI/01/0145/FERDER/007728.

Disclosure

The authors report no conflicts of interest in this work.