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Isoxyl particles for pulmonary delivery: In vitro cytotoxicity and potency
Chenchen Wang1, Anthony J Hickey
1Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Division of Molecular Pharmaceutics, Campus Box #7571, 1310 Kerr Hall, Chapel Hill, NC 27599, United States.
Abstract:
Pulmonary delivery of isoxyl may increase drug efficacy by targeting alveolar macrophages which are host cells for Mycobacteria. Isoxyl microparticles (1-2microm) were obtained by antisolvent precipitation and simultaneous spray drying method. The controls were made by mixing isoxyl solution in DMSO with cell culture media. Depending on the drug concentration, either isoxyl solution or nanosuspension was obtained in these controls. In the study, MTT (methylthiazol tetrazolium) and LDH (lactose dehydrogenase) assays were utilized to test cytotoxicity of these particle suspensions or solutions toward macrophages. Isoxyl microparticles and controls in concentrations up to 100microg/ml were not toxic to macrophages. Both isoxyl microparticle suspensions and controls showed bactericidal activity, as estimated by death of mycobacteria inside the macrophages, at a concentration of 5microg/ml.
Insights
Pulmonary delivery of isoxyl microparticles targets alveolar macrophages for increased efficacy against Mycobacteria. Studies confirmed isoxyl microparticles are non-toxic to macrophages and exhibit bactericidal activity.
Area of Science:
- Pharmacology
- Drug Delivery
- Immunology
Background:
- Pulmonary drug delivery offers targeted treatment for respiratory diseases.
- Alveolar macrophages are crucial host cells for Mycobacteria.
- Isoxyl is a potential therapeutic agent for mycobacterial infections.
Purpose of the Study:
- To evaluate the efficacy and safety of pulmonary delivered isoxyl microparticles.
- To investigate the targeting of alveolar macrophages by isoxyl.
- To assess the bactericidal activity of isoxyl against intracellular Mycobacteria.
Main Methods:
- Isoxyl microparticles were prepared using antisolvent precipitation and spray drying.
- Cytotoxicity was assessed using MTT (methylthiazol tetrazolium) and LDH (lactose dehydrogenase) assays on macrophages.
- Bactericidal activity was determined by monitoring the death of Mycobacteria within macrophages.
Main Results:
- Isoxyl microparticles and control solutions were non-toxic to macrophages at concentrations up to 100 µg/ml.
- Both isoxyl microparticle suspensions and controls demonstrated bactericidal activity at 5 µg/ml.
- The study confirmed the feasibility of using isoxyl microparticles for pulmonary delivery.
Conclusions:
- Pulmonary delivery of isoxyl microparticles is a safe and effective strategy for treating mycobacterial infections.
- Isoxyl microparticles can effectively target alveolar macrophages, enhancing drug efficacy.
- Further research is warranted to explore the clinical applications of isoxyl microparticles.
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