Sustained Bronchodilation with Isoproterenol Poly(Glycolide-co-Lactide) Microspheres

摘要: An animal study was carried out to evaluate the in vivo bronchodilator action of isoproterenol (Iso) from poly(glycolide-co-lactide) (PGL) microspheres. Microspheres with a mean diameter 4.5 µm and drug load 7% were administered intratracheally Long-Evans rats. The microspheres released about 70% incorporated instillation medium before administration, which provided immediate action, remaining 30% available for sustained release. A total 120 animals anesthetized, paralyzed, artificially ventilated, divided into 15 groups (n = 8): 3 each saline, blank microspheres, free Iso, microencapsulated Iso. All instillations made volume 1 ml/kg dose all Iso preparations 0.1 mg/kg. At 3, 6, or 12 hr after intratracheal instillation, serotonin challenge (40 µg/rat) intravenously constrict airways. Airway function tests performed at time interval on one group by maximal expiratory flow-volume maneuver. heart rate receiving formulations similar that saline control group, indicating minimal systemic effect administered. serum levels below 2 ng/ml groups. Animals encapsulated resisted least still present over this period time. On other hand, serotonin-induced airway constriction observed controls points. results clearly show only small fraction is required sustained-release form prolonged pharmacological effect, resulting 50- 100-fold reduction