Optimization of Spray-Drying Conditions and Pharmacodynamics Study of Theophylline/Chitosan/β-Cyclodextrin Microspheres

Abstract

Theophylline has been reported to have considerable pharmacological activity for asthma, which is partly mediated by the anti-inflammatory effects of theophylline. Nevertheless, the wide application of theophylline was hampered due to its rapid metabolization and the poor patient compliance. Microspheres can be applied as targeted and sustained drug-release carriers. The purposes of the present study were to optimize spray-drying conditions and summarize the anti-asthma pharmacodynamics of the theophylline/chitosan/β-cyclodextrin microspheres. The yield, encapsulation efficiency, drug load, and water content were evaluated using ultraviolet spectrophotometry. The morphology of microspheres was observed by scanning electron microscope. Histopathological assessment of microspheres in a murine model of asthma was measured by H&E staining and immunohistochemistry. Levels of IL-4 and TNF-α protein in bronchoalveolar lavage fluid were measured using enzyme-linked immunosorbent assays. The optimal spray-drying conditions (T _gi = 150°C, W _ff = 8 mL/min, W _af = 400 m³/h, and M _w  = 13 × 10⁵) were selected by orthogonal experiment. The yield, encapsulation efficiency, drug load, and water content of the microspheres were 39.3 ± 1.2%, 76.0 ± 0.8%, 19.5 ± 1.5%, and 10.3 ± 0.6%, respectively. A scanning electron micrograph showed that the microspheres were predominantly spherical with smooth surface or slightly wrinkled. Theophylline/chitosan/β-cyclodextrin microspheres markedly decreased the number of infiltrated inflammatory cells, the levels of IL-4, and TNF-α protein in animal models. Based on lung histopathological studies, inflammatory cells, goblet cells, and NF-κB positive cells were inhibited in the theophylline/chitosan/β-cyclodextrin microspheres group compared with those in the model group. These results indicate that optimized theophylline/chitosan/β-cyclodextrin microspheres may be useful as a novelty pulmonary drug-delivery system in therapy for the treatment of bronchial asthma.

Keywords:

• Chitosan
• Microspheres
• Pharmacological actions
• Spray-drying
• Theophylline

Notes

Zhan Qin Feng and Chang Gang Sun contributed equally to this article.

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