Liposomal formulations of oxybutynin and resiniferatoxin for the treatment of urinary diseases: improvement of drug tolerance upon intravesical.

Abstract

The use of liposomes for drug release has demonstrated to be a promising therapeutic platform for biomedical applications. In this study, intravesical administration of OXI (1.5mM) and RTX (100nM) was used to compare histological changes caused in Wistar female rats by the drugs both unloaded and loaded in liposomes. After instillation of formulations by intravesical catheter, bladders were removed and histological analysis carried out at pre-determined time intervals over a period of 60days. Urinalysis was performed to verify the presence of infection and of liposomes. Results showed that RTX caused a higher bladder damage, with inflammatory reaction that reached all bladder layers. After 60days, RTX-treated group showed urothelial alterations, collagen replacement by fibrosis and also abdominal adherence, but not the OXI-treated group. At the end of the assay, the liposomal-treated groups showed a minimal inflammatory reaction and significantly increased bladder size. Moreover, urinalysis confirmed the presence of liposomes in rat urine. RTX promoted higher bladder damage than OXI. Intravesical administration of liposomal OXI or RTX formulations minimized inflammatory reaction, with an extended drug effect on bladders. After a single intravesical administration, liposomes were found in rat urine samples after 60days.