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

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 (1.5 mM) and RTX (100 nM) 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 60 days. 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 60 days, 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 60 days.

Decreased inflammatory response in rat bladder after intravesical administration of capsaicin-loaded liposomes.

The objective of this work was to study the reduction in the capsaicin toxicity by encapsulation in liposomes. Capsaicin was extracted from peppers and characterized with high performance liquid chromatography (HPLC). We determined the zeta potential, polydispersivity index (PdI) and vesicle size of liposomes. Wistar rats were submitted to intravesical instillation of liposomes (LIP), capsaicin (CAP) or liposomes with capsaicin (CAPLIP). After 24 hours, bladders were removed for histological analysis. Vesicle size ranged from 68 to 105 nm with PdI smaller than 0.2 and zeta potential around -30 mV. The vesicles maintained stability over the 14-day study. The histological analysis of the CAP group showed intense inflammation in almost all bladder layers, as well as ulcer formation. Conversely, the CAPLIP group showed a smooth inflammatory reaction and hyperemia. In conclusion, the liposomes effectively protected the bladder against the irritative action of capsaicin.