Dry powder inhalation formulation of chitosan nanoparticles for co-administration of isoniazid and pyrazinamide

Abstract

Co-loaded isoniazid and pyrazinamide chitosan nanoparticles were formulated using the ionic gelation method. The formulations were adjusted to five mass ratios of tripolyphosphate (TPP) and chitosan at three TPP concentrations. Particle size, polydispersity index, zeta potential, and encapsulation efficiency were used to evaluate all formulations. The results revealed that the ratio of TPP to chitosan had the highest impact in generating chitosan nanoparticles. The selected nanoparticle formulations were freeze-dried, and the obtained dry powders were characterized using scanning electron microscopy, differential scanning calorimetry, X-ray diffraction, and Fourier-transform infrared spectroscopy to confirm the interaction of loaded drug and formulation excipients. The aerosolized performance of dry powders was also evaluated using the Andersen cascade impactor. A mass median aerodynamic diameter of 3.3–3.5 µm, % fine particle fraction of 30–44%, and 92–95% emitted dose were obtained from all formulations. The dry powder formulations were not toxic to the respiratory tract cell lines. Furthermore, they did not provoke alveolar macrophages into producing inflammatory cytokines or nitric oxides, indicating that the formulations are safe and could potentially be used to deliver to respiratory tract for tuberculosis treatment.

Keywords:

• Isoniazid
• pyrazinamide
• chitosan
• ionic gelation
• dry powder aerosols

Acknowledgements

Some parts of this work were carried out at the Drug Delivery System Excellent Center (DDSEC), Prince of Songkhla University. The authors would like to acknowledge Prof. Dr. Teerapol Srichana for his generous support and valuable advice throughout the project. We are especially thankful to Mr. Ekawat Tawithong and Ms. Titpawan Nakpheng for their technical and scientific support and suggestions.

Disclosure statement

No potential conflict of interest was reported by the authors

Additional information

Funding

This work was funded by Rangsit University [grant number 7/2562].