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Spray-dried lactose-leucine microparticles for pulmonary delivery of antimycobacterial nanopharmaceuticals

  • Pulmonary delivery of nanocarriers for novel antimycobacterial compounds is challenging because the aerodynamic properties of nanomaterials are sub-optimal for such purposes. Here, we report the development of dry powder formulations for nanocarriers containing benzothiazinone 043 (BTZ) or levofloxacin (LVX), respectively. The intricacy is to generate dry powder aerosols with adequate aerodynamic properties while maintaining both nanostructural integrity and compound activity until reaching the deeper lung compartments. Microparticles (MPs) were prepared using vibrating mesh spray drying with lactose and leucine as approved excipients for oral inhalation drug products. MP morphologies and sizes were measured using various biophysical techniques including determination of geometric and aerodynamic mean sizes, X-ray diffraction, and confocal and focused ion beam scanning electron microscopy. Differences in the nanocarriers’ characteristics influenced the MPs’ sizes and shapes, their aerodynamic properties, and, hence, also the fraction available for lung deposition. Spay-dried powders of a BTZ nanosuspension, BTZ-loaded silica nanoparticles (NPs), and LVX-loaded liposomes showed promising respirable fractions, in contrast to zirconyl hydrogen phosphate nanocontainers. While the colloidal stability of silica NPs was improved after spray drying, MPs encapsulating either BTZ nanosuspensions or LVX-loaded liposomes showed the highest respirable fractions and active pharmaceutical ingredient loads. Importantly, for the BTZ nanosuspension, biocompatibility and in vitro uptake by a macrophage model cell line were improved even further after spray drying.

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Document Type:Article
Author:Durairaj Thiyagarajan, Benedikt C. HuckORCiD, Birgit Nothdurft, Marcus Koch, David Rudolph, Mark Rutschmann, Claus Feldmann, Constantin HozsaORCiD, Marcus Furch, Karen F. W. Besecke, Robert K. Gieseler, Brigitta LoretzORCiD, Claus-Michael LehrORCiD
Parent Title (English):Drug Delivery and Translational Research
First Page:1766
Last Page:1778
Year of first Publication:2021
Release Date:2022/11/18
Tag:antibacterial nanoparticles; benzothiazinone; dry powder formulations; levofloxacin; liposomes; respiratory infections; tuberculosis
Impact:05.671 (2021)
Funding Information:Helmholtz-Zentrum für Infektionsforschung GmbH (HZI)
Research Groups:Physical Analytics
Open Access:Open Access
Signature:INM 2021/070
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International