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Ethambutol-Loaded Solid Lipid Nanoparticles as Dry Powder Inhalable Formulation for Tuberculosis Therapy

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Abstract

Ethambutol hydrocloride (EMB) is an anti-tuberculosis drug, which is commonly used as a protection agent against of unrecognized resistance to other drugs employed to treat this disease. Since oral form of EMB has some side effects and cellular toxicity, direct administration of EMB into lungs seems to be an attractive and reasonable option in order to overcome these side effects. Our main goal in this study was assessment of pulmonary administration through dry powder inhaler (DPI) using EMB-loaded solid lipid nanoparticles (SLNs). We prepared EMB-loaded SLNs using two techniques (hot homogenization and ultrasonication). DPI formulations were made by spray drying of EMB-loaded SLNs with and without mannitol. For investigation of flowbility of the prepared powders, Carr’s index and Hausner ratio, and for in vitro deposition of the powders, Next Generation Impactor (NGI) analysis were used. The encapsulation efficiency and particle size of obtained particles were higher than 98% and sub-100 nm, respectively. Toxicity investigation of EMB-loaded SLNs via MTT assay showed biocompatibility and non-toxicity of the SLNs. Results of flowability and aerodynamic traits assessment of EMB-loaded SLN DPI powder confirmed the suitability of prepared powders. Overall, the attained results showed that EMB-loaded SLN DPI has high potential for direct treatment of tuberculosis.

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Acknowledgments

The authors would like to thank the Research Center for Pharmaceutical Nanotechnology (RCPN), Tabriz University of Medical Sciences for supporting this project (grant no. 5/23769).

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Authors and Affiliations

  1. Immunology Research Center, Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

    Elham Nemati, Ahad Mokhtarzadeh & Ali Mohammadi

  2. Department of Biotechnology, Higher Education Institute of Rab-Rashid, Tabriz, Iran

    Elham Nemati

  3. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Vahid Panahi-Azar, Hamed Hamishehkar, Mehran Mesgari-Abbasi & Jafar Ezzati Nazhad Dolatabadi

  4. Department of Analytical Chemistry, University of Valencia, Dr. Moliner 50, 46100, Burjassot, Valencia, Spain

    Miguel de la Guardia

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  1. Elham Nemati
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  2. Ahad Mokhtarzadeh
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  4. Ali Mohammadi
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Correspondence to Jafar Ezzati Nazhad Dolatabadi or Miguel de la Guardia.

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Nemati, E., Mokhtarzadeh, A., Panahi-Azar, V. et al. Ethambutol-Loaded Solid Lipid Nanoparticles as Dry Powder Inhalable Formulation for Tuberculosis Therapy. AAPS PharmSciTech 20, 120 (2019). https://doi.org/10.1208/s12249-019-1334-y

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