Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Preclinical Efficacy and Side Effects with Inhaled Corticosteroids Nanosuspension Formulations | Nanoscale Res Lett 2010 5 1010-1019 DOI s11671-010-9597-y NANO EXPRESS Evaluating the Suitability of Using Rat Models for Preclinical Efficacy and Side Effects with Inhaled Corticosteroids Nanosuspension Formulations Po-Chang Chiang Yiding Hu Jason D. Blom David C. Thompson Received 4 March 2010 Accepted 29 March 2010 Published online 10 April 2010 The Author s 2010. This article is published with open access at Abstract Inhaled corticosteroids ICS are often prescribed as first-line therapy for patients with asthma Despite their efficacy and improved safety profile compared with oral corticosteroids the potential for systemic side effects continues to cause concern. In order to reduce the potential for systemic side effects the pharmaceutical industry has begun efforts to generate new drugs with pulmonary-targeted topical efficacy. One of the major challenges of this approach is to differentiate both efficacy and side effects pulmonary vs. systemic in a preclinical animal model. In this study fluticasone and ciclesonide were used as tool compounds to explore the possibility of demonstrating both efficacy and side effects in a rat model using pulmonary delivery via intratracheal IT instillation with nanosuspension formulations. The inhibition of neutrophil infiltration into bronchoalveolar lavage fluid BALF and cytokine TNFa production were utilized to assess pulmonary efficacy while adrenal and thymus involution as well as plasma corticosterone suppression was measured to assess systemic side effects. Based on neutrophil infiltration and cytokine production data the ED50s for ciclesonide and fluticasone were calculated to be and mg respectively. At the ED50 the average adrenal involution was for ciclesonide versus for fluticasone while the average thymus involution was for ciclesonide versus for fluticasone. However the differentiation became less significant when the dose was pushed to the EDmax
