การเตรียมไพราซินาไมด์และลีโวฟลอกซาซินโปรลิโปโซม และความเป็นไปได้ในการรักษาวัณโรคปอด

Thesis (Ph.D., Pharmaceutical Sciences)--Prince of Songkla University, 201

การพัฒนาตำรับ Bacillus megaterium ในรูปแบบแกรนนูลและเม็ดเพื่อควบคุมโรคกาบใบแห้งของข้าว

Thesis (M.Pharm., Pharmaceutical Sciences)--Prince of Songkla University, 200

Isoniazid Proliposome Powders for Inhalation—Preparation, Characterization and Cell Culture Studies

The aims of this study were to develop proliposome powders containing isoniazid (INH) in a dry powder aerosol form. INH-proliposome powders were prepared by a spray drying method. Proliposome physicochemical properties were determined using cascade impactor, X-ray diffraction and differential scanning calorimetry. The toxicity of proliposomes to respiratory-associated cell lines and its potential to provoke immunological responses from alveolar macrophages (AM) were determined. Free INH and INH-proliposome bioactivities were tested in vitro and in AM infected with Mycobacterium bovis (M. bovis). Aerosolization properties of INH-proliposome powders at 60 L/min, the powders showed mass median aerodynamic diameters of 2.99–4.92 mm, with fine particle fractions (aerosolized particles less than 4.4 µm) of 15–35%. Encapsulation of INH was 18–30%. Proliposome formulations containing INH to mannitol ratios of 4:6 and 6:4 exhibited the greatest overlapping peak between the drug and mannitol. INH-proliposomes were evidently nontoxic to respiratory-associated cells, and did not activate AM to produce inflammatory mediators—including interleukin-1b (IL-1b), tumor necrosis factor-a (TNF-a), and nitric oxide—at a toxic level. The efficacy of INH-proliposome against AM infected with M. bovis was significantly higher than that of free INH (p < 0.05). INH-proliposomes are potential candidates for an alternative tuberculosis treatment

Isoniazid Proliposome Powders for Inhalation—Preparation, Characterization and Cell Culture Studies

Abstract: The aims of this study were to develop proliposome powders containing isoniazid (INH) in a dry powder aerosol form. INH-proliposome powders were prepared by a spray drying method. Proliposome physicochemical properties were determined using cascade impactor, X-ray diffraction and differential scanning calorimetry. The toxicity of proliposomes to respiratory-associated cell lines and its potential to provoke immunological responses from alveolar macrophages (AM) were determined. Free INH and INH-proliposome bioactivities were tested in vitro and in AM infected with Mycobacterium bovis (M. bovis). Aerosolization properties of INH-proliposome powders at 60 L/min, the powders showed mass median aerodynamic diameters of 2.99–4.92 �m, with fine particle fractions (aerosolized particles less than 4.4 µm) of 15–35%. Encapsulation of INH was 18–30%. Proliposome formulations containing INH to mannitol ratios of 4:6 and 6:4 exhibited the greatest overlapping peak between the drug and mannitol. INH-proliposomes were evidently nontoxic to respiratory-associated cells, and did not activate AM to produce inflammatory mediators—including interleukin-1 � (IL-1�), tumor necrosis factor-� (TNF-�), and nitric oxide—at a toxic level. The efficacy of INH-proliposome against A

Levofloxacin-Proliposomes: Opportunities for Use in Lung Tuberculosis

Levofloxacin (LEV) is a relatively new-generation fluoroquinolone antibiotic that has good activity against &lt;em&gt;Mycobacterium tuberculosis&lt;/em&gt;. 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 &lt;em&gt;&lt;em&gt;infrared&lt;/em&gt;&lt;/em&gt;&lt;em&gt; &lt;/em&gt;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 &lt;em&gt;in vivo&lt;/em&gt; 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 &lt;em&gt;M. bovis&lt;/em&gt; of LEV and LEV-proliposomes containing LEV 10% were 1 and 0.5 µg/mL, respectively. The efficacy of LEV-proliposomes against &lt;em&gt;M. bovis&lt;/em&gt; was significantly higher than that of free LEV (&lt;em&gt;p&lt;/em&gt; &lt; 0.05). The efficacy of the LEV-proliposomes against &lt;em&gt;M. tuberculosis&lt;/em&gt; 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