Effects of Local Budesonide Treatment on the Cell-Mediated Immune Response in Acute and Relapsing Colitis in Rats

Glucocorticosteroids (GCS) are effective intreatment of inflammatory bowel disease (IBD), but alsohave unwanted systemic side effects. Here, we describethe effects of budesonide and dexamethasone on acute experimental colitis and on T cells inthymus and spleen, as well as the effect of budesonidetreatment on relapsing colitis. Acute colitis wasinduced by intracolonic administration of2,4,6-trinitrobenzene sulfonic acid (TNBS) in ethanol, and a relapsewas induced by an intraperitoneal booster of TNBS. GCSwere administered intrarectally on days 1, 4, and 6after induction of acute colitis or a relapse.Inflammatory cells in the colon were studied on day 7, andin acute colitis also on days 13 and 16. Budesonidetreatment in acute and relapsing colitis resulted inreduction of macroscopic damage and decreased thenumbers of macrophages and neutrophils in the colon.Dexamethasone was less effective. Dexamethasone, but notbudesonide, reduced the number of T cells in the thymus.It is concluded that local budesonide is more effective in treatment of acute experimentalcolitis than dexamethasone and, in contrast todexamethasone, did not cause a general suppression of Tcells. Although budesonide was very effective in thetreatment of relapsing colitis, this effect was notaccomplished by affecting the number of T cells in thecolon.     

Preparation of Budesonide-Loaded Polycaprolactone Nanobeads by Electrospraying for Controlled Drug Release

Corticosteroids such as budesonide are the drugs of choice for the treatment of inflammatory disorders with an inherent limitation, viz., rapid elimination. To overcome this constraint and attain sustained release, budesonide was encapsulated in a biodegradable polymer, polycaprolactone (PCL), by DC electrospraying. By varying the experimental parameters involved in electrospraying such as applied voltage, flow rate, viscosity as well as conductivity of the polymer solution, the dimensionality of nanostructures was tuned from 1-D nanofibers to spherical nanoparticles. By adopting this rapid and viable method of DC electrospraying, we successfully prepared aqueous suspensions of nearly monodispersed, nano-sized drug encapsulated PCL. Drug encapsulation efficiency, in vitro drug release as well as biocompatibility studies of budesonide-loaded PCL nanobeads were carried out. The cytocompatible nanobeads prepared by electrospraying exhibited good encapsulation efficiency (approx. 75%), with controlled drug release enabled by the dissolution of the polymer. Our results demonstrate the potential of this novel technique of electrospraying in developing efficient drug encapsulated polymeric nanocarriers possessing sustained drug release profile.