Chondroitin sulphate microparticles as antitubercular drug carriers

Susan Rodrigues

Chondroitin sulphate microparticles as antitubercular drug carriers

Susana Rodrigues1,2, Francesca Buttini3, Lea Ann Dailey4, Leonor Faleiro1, Ana M. Rosa da Costa5 & Ana Grenha1,2

1CBMR – Centre for Biomedical Research Drug Delivery Laboratory, University of Algarve, Campus de Gambelas, Faro, 8005-139, Portugal

2CCMAR – Centre of Marine Sciences, University of Algarve, Campus de Gambelas, Faro, 8005-139, Portugal

3 Department of Food and Drug Science, University of Parma, Parma, Italy

4Biopharmacy group, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany

5CIQA – Algarve Chemistry Research Center and Department of Chemistry and Pharmacy, Faculty of Sciences and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal


Tuberculosis remains a deadly pathology and new therapeutic strategies are demanded. Considering that the lung is the primary site of infection, direct lung delivery of antibiotics is an interesting and, possibly, effective approach. The strategy requires developing carriers with aerodynamic properties ensuring drug delivery in the alveoli, where bacteria are hosted by macrophages. Ability to promote macrophage capture and intracellular accumulation of drugs is also desired. In this work, we propose inhalable spray-dried chondroitin sulphate microparticles with suitable aerodynamic properties to reach the alveoli. Macrophage targeting is expected to be mediated by microparticle size and by the content in chondroitin sulphate. The polysaccharide has alternating units of sulphated N-acetylgalactosamine and glucuronic acid residues, the former being recognized by macrophage receptors. Chondroitin sulphate microparticles associating isoniazid and rifabutin in combination were produced with yields above 70%. The aerodynamic characterisation of microparticles, with mass median aerodynamic diameter of 3.8 µm and fine particle fraction of 43%, indicates adequate properties for deep lung delivery. Drug-loaded microparticles do not have a cytotoxic effect on alveolar epithelial cells (A549) or macrophage cell lines (THP-1 and J774A.1). The bactericidal capacity of the drugs against Mycobacterium bovis was not affected by the encapsulation process. Notwithstanding the good indication of these results, it is considered very important to extend the type of assays to be performed. The results obtained so far are considered encouraging towards the objective of establishing the potential of chondroitin sulphate microparticles as inhalable carriers in tuberculosis treatment.

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