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

I-Hsuan Yang; I-En Lin; Ya-Jyun Liang; Jhih-Ni Lin; Tzu-Chien Chen; Zhi-Yu Chen; Che-Yung Kuan; Chih-Ying Chi; Chi-Han Li; Hung-Ming Wu; Feng-Huei Lin

doi:10.1002/btm2.10267

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

Bioeng Transl Med. 2021 Dec 4;7(2):e10267. doi: 10.1002/btm2.10267. eCollection 2022 May.

Authors

I-Hsuan Yang¹, I-En Lin¹, Ya-Jyun Liang¹, Jhih-Ni Lin¹, Tzu-Chien Chen¹, Zhi-Yu Chen¹, Che-Yung Kuan^{1

2}, Chih-Ying Chi^{2

3}, Chi-Han Li^{2

3}, Hung-Ming Wu⁴, Feng-Huei Lin^{1

2

3}

Affiliations

¹ Department of Biomedical Engineering College of Medicine and College of Engineering, National Taiwan University Taipei Taiwan.
² Institute of Biomedical Engineering and Nanomedicine National Health Research Institutes Zhunan, Miaoli County Taiwan.
³ PhD Program in Tissue Engineering and Regenerative Medicine National Chung Hsing University Taichung Taiwan.
⁴ Department of Neurology Changhua Christian Hospital Changhua Taiwan.

Abstract

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.

Keywords: di(2‐ethylhexyl) phthalate; menopausal syndrome; mucoadhesive gel; thioglycolic acid immobilized chitosan.