Inhalable Spray-Dried Chondroitin Sulphate Microparticles: Effect of Different Solvents on Particle Properties and Drug Activity.

Susana Rodrigues,Ana Da Costa,María Torres,Ana Grenha,Noelia Flórez-Fernández,Francesca Buttini,Maria Faleiro

doi:10.3390/polym12020425

Susana Rodrigues, Ana Da Costa + Show 5 more

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https://doi.org/10.3390/polym12020425

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Abstract

Spray-drying stands as one of the most used techniques to produce inhalable microparticles, but several parameters from both the process and the used materials affect the properties of the resulting microparticles. In this work, we describe the production of drug-loaded chondroitin sulphate microparticles by spray-drying, testing the effect of using different solvents during the process. Full characterisation of the polymer and of the aerodynamic properties of the obtained microparticles are provided envisaging an application in inhalable tuberculosis therapy. The spray-dried microparticles successfully associated two first-line antitubercular drugs (isoniazid and rifabutin) with satisfactory production yield (up to 85%) and drug association efficiency (60%–95%). Ethanol and HCl were tested as co-solvents to aid the solubilisation of rifabutin and microparticles produced with the former generally revealed the best features, presenting a better ability to sustainably release rifabutin. Moreover, these presented aerodynamic properties compatible with deep lung deposition, with an aerodynamic diameter around 4 μm and fine particle fraction of approximately 44%. Finally, it was further demonstrated that the antitubercular activity of the drugs remained unchanged after encapsulation independently of the used solvent.

Highlights

Polysaccharides have been frequently used as matrix materials of inhalable microparticles aimed at lung drug delivery and spray-drying is a predominant technique applied in their production
The purified polymer was used to prepare microparticles loaded with a combination of INH and RFB
As far as we know, this is the first time that chondroitin sulphate (ChS) is being proposed as a platform for the inhalable therapy of tuberculosis

Summary

Introduction

Polysaccharides have been frequently used as matrix materials of inhalable microparticles aimed at lung drug delivery and spray-drying is a predominant technique applied in their production. Chondroitin sulphate (ChS) is a natural polymer commonly found on proteoglycans in several tissues, including the lungs [1]. It is composed of alternating sulphated N-acetylgalactosamine and glucuronic acid residues, both referred to be recognised by macrophage receptors [2,3], which provides an important advantage in macrophage targeting strategies [4]. Direct lung delivery of the antibiotics could, bring advantages over conventional oral therapy, as it co-localises drugs and pathogenic agents in the same compartment. To be optimised to reach the alveoli, where macrophages are located

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