Pharmaceutics (Aug 2012)

Levofloxacin-Proliposomes: Opportunities for Use in Lung Tuberculosis

  • Teerapol Srichana,
  • Niracha Yanyium,
  • Ekawat Thawithong,
  • Titpawan Nakpheng,
  • Wipaporn Rojanarat

DOI
https://doi.org/10.3390/pharmaceutics4030385
Journal volume & issue
Vol. 4, no. 3
pp. 385 – 412

Abstract

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Levofloxacin (LEV) is a relatively new-generation fluoroquinolone antibiotic that has good activity against <em>Mycobacterium tuberculosis</em>. The aims of this study were to develop and evaluate LEV-proliposomes in a dry powder aerosol form for pulmonary delivery. LEV-proliposomes containing LEV, soybean phosphatidylcholine, cholesterol and porous mannitol were prepared by a spray drying technique. The physicochemical properties of LEV-proliposomes were determined using a cascade impactor, X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier transform <em><em>infrared</em></em><em> </em>spectroscopy (FT-IR). The toxicity of proliposomes to respiratory-associated cell lines and its potential to provoke immunological responses from alveolar macrophages (AMs) were evaluated. Antimycobacterial activity using flow cytometry and an <em>in vivo</em> repeated dose toxicity test in rats were carried out. LEV-proliposomes were successfully prepared with mass median aerodynamic diameters of 4.15–4.44 μm and with fine particle fractions (aerosolized particles of less than 4.4 µm) of 13%–38% at 60 L/min. LEV-proliposomes were less toxic to respiratory-associated cells than LEV, and did not activate AMs to produce inflammatory mediators that included interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and nitric oxide. The minimum inhibitory concentration (MIC) against <em>M. bovis</em> of LEV and LEV-proliposomes containing LEV 10% were 1 and 0.5 µg/mL, respectively. The efficacy of LEV-proliposomes against <em>M. bovis</em> was significantly higher than that of free LEV (<em>p</em> < 0.05). The efficacy of the LEV-proliposomes against <em>M. tuberculosis</em> was equal to that of the free LEV (MIC = 0.195 µg/mL). In a repeated dose toxicity study in rats, renal and liver toxicity was not observed. LEV-proliposomes should now be tested as an alternative formulation for delivering LEV to the lower airways.

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