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Levofloxacin-Proliposomes: Opportunities for Use in Lung Tuberculosis
Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand
Drug Delivery System Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand
Department of Pharmacology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand
* Author to whom correspondence should be addressed.
Received: 8 May 2012; in revised form: 5 July 2012 / Accepted: 26 July 2012 / Published: 13 August 2012
Abstract: Levofloxacin (LEV) is a relatively new-generation fluoroquinolone antibiotic that has good activity against Mycobacterium tuberculosis. 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 infrared 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 in vivo 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 M. bovis of LEV and LEV-proliposomes containing LEV 10% were 1 and 0.5 µg/mL, respectively. The efficacy of LEV-proliposomes against M. bovis was significantly higher than that of free LEV (p < 0.05). The efficacy of the LEV-proliposomes against M. tuberculosis 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.
Keywords: dry powder inhaler; immunological response; levofloxacin; proliposome; tuberculosis
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Rojanarat, W.; Nakpheng, T.; Thawithong, E.; Yanyium, N.; Srichana, T. Levofloxacin-Proliposomes: Opportunities for Use in Lung Tuberculosis. Pharmaceutics 2012, 4, 385-412.
Rojanarat W, Nakpheng T, Thawithong E, Yanyium N, Srichana T. Levofloxacin-Proliposomes: Opportunities for Use in Lung Tuberculosis. Pharmaceutics. 2012; 4(3):385-412.
Rojanarat, Wipaporn; Nakpheng, Titpawan; Thawithong, Ekawat; Yanyium, Niracha; Srichana, Teerapol. 2012. "Levofloxacin-Proliposomes: Opportunities for Use in Lung Tuberculosis." Pharmaceutics 4, no. 3: 385-412.