Systemic administration of budesonide in pegylated liposomes for improved efficacy in chronic rhinosinusitis.

Abstract

Chronic rhinosinusitis (CRS) is a chronic inflammatory condition affecting the nasal and paranasal sinuses of approximately 11.5% of the United States adult population. Oral corticosteroids are effective in controlling sinonasal inflammation in CRS, but the associated adverse effects limit their clinical use. Topical budesonide has demonstrated clinical efficacy in patients with CRS. Herein, we investigated the systemic delivery of liposomes tethered with poly(ethylene glycol) (PEG) and loaded with budesonide in a murine model of CRS. PEGylated liposomes encapsulated with budesonide phosphate (L-BudP) were administered via tail vein injection, and the feasibility of L-BudP to reduce sinonasal inflammation was compared to that of free budesonide phosphate (F-BudP) and topical budesonide phosphate (T-BudP) treatment over a 14-day study period. Compared to a single injection of F-BudP and repeat T-BudP administration, a single injection of L-BudP demonstrated increased and prolonged efficacy, resulting in the significant improvement of sinonasal tissue histopathological scores (p<0.05) with decreased immune cell infiltration (p<0.05). Toxicities associated with L-BudP and T-BudP treatment, assessed via body and organ weight, as well as peripheral blood liver enzyme and differential white blood cell analyses, were transient and comparable. These data suggest that systemic liposomal budesonide treatment results in improved efficacy over topical treatment.