Development and evaluation of a prostate-targeting wild chrysanthemum rectal heating gel for prostatitis treatment

Abstract

This study aimed to develop a rectal heating gel for targeted treatment of prostatitis, on the basis of the synergistic effects of wild chrysanthemum (Chrysanthemu indicum) extract (rich in buddleoside and chlorogenic acid) and a phase-change microemulsion (PCME). A microemulsion system was developed with n-docosane serving as the thermal energy storage medium. The PCME was systematically characterized for particle size, stability, phase transition temperature, as well as heat-retention capacity. Results demonstrated good stability, with a phase transition temperature of 42.94–43.57 °C and latent heat of 98.43–100.41 J/g, capable of sustaining heat release for 30 min under simulated physiological conditions. Upon external heating, the PCME efficiently stored thermal energy; subsequently, following rectal administration, the incorporated system delivered prolonged and gentle thermotherapy at physiological temperature. Sodium carboxymethyl cellulose (CMC-Na) was selected as the mucoadhesive gel matrix to co-load the extract and PCME. Additionally, the optimized formulation contained 8.0 % extract, 75.5 % PCME, 1.2 % CMC-Na, and 15.3 % water. In vitro release studies indicated 69.21 % buddleoside and 93.73 % chlorogenic acid release over 12  h, with mucosal permeation rates of 69.92 % and 93.70 %, respectively. Animal studies revealed no notable irritation to the rectum or prostate, while significantly enhancing drug accumulation and peak concentration within prostatic tissue. Compared to conventional formulations, the heating gel more effectively decreased the prostate index and inhibited inflammatory cytokine expression, underscoring its synergistic efficacy in localized thermotherapy combined with targeted phytomedicine delivery. This innovative gel formulation is structurally stable, easy to administer, and dual-functional, representing a promising therapeutic candidate for the management of chronic prostatitis.