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Updated: May 18, 2026
Harvesting Murine Alveolar Macrophages and Evaluating Cellular Activation Induced by Polyanhydride Nanoparticles
Published on: June 8, 2012
Inhaled pyrazinamide proliposome for targeting alveolar macrophages
Wipaporn Rojanarat1, Titpawan Nakpheng, Ekawat Thawithong
1Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
Objective:
In this study, pyrazinamide (PZA)-proliposome in a dry powder aerosol form was developed for delivering drugs to alveolar macrophages (AMs) infected with mycobacteria.
Materials And Methods:
PZA-proliposomes consisting of pyrazinamide, soybean phosphatidylcholine, cholesterol and porous mannitol were prepared by a spray drying method. The PZA-proliposome physicochemical properties were determined using a cascade impactor, X-ray diffraction, differential scanning calorimetry and infrared spectroscopy. The toxicity of proliposomes to respiratory-associated cell lines (Calu-3, A549 and NR8383) and its potential to provoke immunological responses from AMs were determined. In vivo repeated dose toxicity in rats was evaluated.
Results And Discussion:
PZA-proliposomes were successfully prepared. For the aerosolization properties of PZA-proliposomes at 60 l/min, the powders showed mass median aerodynamic diameters of 4.26-4.39 µm, with fine particle fractions (aerosolized particles less than 4.4 µm) of 20-30%. Encapsulation of PZA was 26-45%. PZA-proliposomes were less toxic to respiratory-associated cells, and did not activate AMs to produce inflammatory mediators, including interleukin-1β, tumor necrosis factor-α, and nitric oxide, at a toxic level. Renal and liver toxicity in rats were not observed.
Conclusions:
We suggest that PZA-proliposomes are potential candidates for pulmonary tuberculosis treatment.
Insights
Pyrazinamide (PZA)-proliposomes were developed as an aerosol powder for treating lung infections. This novel drug delivery system showed low toxicity and potential for pulmonary tuberculosis treatment.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Pulmonary Medicine
Background:
- Tuberculosis remains a significant global health challenge, necessitating innovative treatment strategies.
- Targeted delivery of anti-tubercular drugs to infected alveolar macrophages (AMs) can enhance efficacy and reduce systemic toxicity.
- Pyrazinamide (PZA) is a crucial first-line anti-tubercular drug, but its delivery to the lungs can be challenging.
Purpose of the Study:
- To develop pyrazinamide (PZA)-proliposomes in a dry powder aerosol form for targeted delivery to AMs.
- To characterize the physicochemical properties and aerosolization performance of the PZA-proliposomes.
- To evaluate the in vitro and in vivo toxicity of the PZA-proliposomes.
Main Methods:
- PZA-proliposomes were prepared using a spray-drying method with pyrazinamide, soybean phosphatidylcholine, cholesterol, and porous mannitol.
- Physicochemical properties were assessed using cascade impaction, X-ray diffraction, differential scanning calorimetry, and infrared spectroscopy.
- In vitro cytotoxicity assays on respiratory cell lines (Calu-3, A549, NR8383) and immunological response assessments in AMs were performed. In vivo toxicity studies in rats were also conducted.
Main Results:
- Successfully prepared PZA-proliposomes with PZA encapsulation efficiencies ranging from 26-45%.
- Aerosolization studies showed mass median aerodynamic diameters of 4.26-4.39 µm, with fine particle fractions of 20-30% at 60 l/min.
- PZA-proliposomes exhibited reduced toxicity to respiratory cells and did not induce significant inflammatory responses in AMs. No renal or liver toxicity was observed in rats.
Conclusions:
- PZA-proliposomes are successfully prepared and demonstrate favorable aerosolization properties.
- The developed PZA-proliposomes show a promising safety profile with low cytotoxicity and minimal immunogenicity.
- PZA-proliposomes represent a potential advanced drug delivery system for the effective treatment of pulmonary tuberculosis.
