Development of di(2-ethylhexyl) phthalate-containing thioglycolic acid immobilized chitosan mucoadhesive gel as an alternative hormone therapy for menopausal syndrome.

Menopausal syndrome includes the symptoms that most women experience owing to hormone changes after menopause. Although hormone replacement therapy is a common treatment for menopausal syndrome, there are still many side effects and challenges hindering research. In this study, thioglycolic acid (TGA)-immobilized chitosan mucoadhesive gel was synthesized by a new method of low concentration of 1,4-butanediol diglycidyl ether (BDDE) would encapsulate di(2-ethylhexyl) phthalate (DEHP) as an alternative hormone replacement therapy for menopausal syndrome. The efficacies of the DEHP-containing TGA-chitosan gel (CT-D) were confirmed and evaluated by materials characterization and in vitro study. Results showed that CT-D was not cytotoxic and had better mucoadhesive ability than chitosan. The animal model was constructed 1 month after bilateral ovariectomy in SD rats. CT-D was administered intravaginally every 3 days. Bodyweight, wet weight of the uterus and vagina, vaginal smears, histology, blood element analysis, and serological analysis was used to assess the ability of the material to relieve menopausal syndrome. The results indicated that the combination of the sustained release of DEHP and mucoadhesive TGA-immobilized chitosan allows the developed CT-D to relieve the menopausal syndrome through low concentrations of DEHP, which falls in the safety level of the tolerable daily intake of DEHP.

Synthesis, characterization, and evaluation of BDDE crosslinked chitosan-TGA hydrogel encapsulated with genistein for vaginal atrophy.

Vagina atrophy is a common symptom in women after menopause owing to decreasing estrogen levels. The most conventional treatment for this condition is estrogen cream. The shortcoming is its weak adhesion to the vagina mucus, thus requiring frequent daily application. In this study, BDDE was selected to crosslink and graft chitosan with thioglycolic acid, to form thiolated chitosan (CT) and improve the mucoadhesive properties of chitosan. Genistein was selected as the bioactive molecule that could exhibit estrogen-like properties for long-term treatment of vaginal atrophy. The efficacies of the materials were characterized and evaluated both in vitro and in vivo. Results showed that the mucoadhesive property of CT was approximately two-fold stronger against the constant flow than unmodified chitosan. CT with genistein (CT-G) was administered intravaginally every three days in vivo. It showed that the developed CT-G recover 54 % of the epithelium thickness of an atrophic vagina and ease vaginal atrophy.