Glycyrrhizic acid and its carrier-free micellar formulation: Unraveling the potential for enhanced oral prevention of hearing loss

Hearing loss, a global health concern, significantly impacts patients with delayed language development, impaired neurocognitive function, and severe social problems. The main cause is the cochlear hair cell damage induced by oxidative stress and inflammation from ototoxic drugs, noise exposure or d...

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Main Authors: Huaan Li, Bohan Lin, Shuangwu Wang, Ying Zhang, Zeming Zhou, Dingsheng Wen, Zhifeng Zhang, Xiaohua Feng, Lu Wen, Jun He, Gang Chen
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:International Journal of Pharmaceutics: X
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590156725000258
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author Huaan Li
Bohan Lin
Shuangwu Wang
Ying Zhang
Zeming Zhou
Dingsheng Wen
Zhifeng Zhang
Xiaohua Feng
Lu Wen
Jun He
Gang Chen
author_facet Huaan Li
Bohan Lin
Shuangwu Wang
Ying Zhang
Zeming Zhou
Dingsheng Wen
Zhifeng Zhang
Xiaohua Feng
Lu Wen
Jun He
Gang Chen
author_sort Huaan Li
collection DOAJ
description Hearing loss, a global health concern, significantly impacts patients with delayed language development, impaired neurocognitive function, and severe social problems. The main cause is the cochlear hair cell damage induced by oxidative stress and inflammation from ototoxic drugs, noise exposure or diabetes. Glycyrrhizic acid (GA), derived from edible herb licorice, is widely utilized in traditional Chinese medicine and clinical treatments for liver diseases. However, its potential in preventing hearing loss remains largely unexplored. Herein, we propose GA as a novel otoprotective agent and demonstrate its capability to prevent hearing loss. Our results show that GA effectively reduces oxidative stress and inflammation induced by cisplatin, aminoglycosides, or even noise and diabetes, thereby protecting cochlear hair cells. In hearing loss models, two commonly used administration methods were compared, with tympanic injection providing better protective effects than oral administration of GA. To enhance oral bioavailability, GA is employed as both the medicine and excipient, and formulated into micelles with curcumin, another extensively used bioactive compound. Interestingly, formulation parameters such as feeding ratio and temperature have little impact on micelle size but significantly affect the drug loading efficiency. The carrier-free strategy can achieve a high drug loading capacity and significantly increase the drug concentration in blood, offering improved preventive efficacy. Notably, the micelles also exhibit protection on kidneys and liver, and do not compromise the antitumor activity of cisplatin. Therefore, GA holds promise as an otoprotective candidate, with potential clinical applications for oral prophylaxis of hearing loss using the micellar formulation.
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spelling doaj-art-c5ecda09cf2245c8b7b49f7cce812aef2025-08-20T03:30:44ZengElsevierInternational Journal of Pharmaceutics: X2590-15672025-06-01910034010.1016/j.ijpx.2025.100340Glycyrrhizic acid and its carrier-free micellar formulation: Unraveling the potential for enhanced oral prevention of hearing lossHuaan Li0Bohan Lin1Shuangwu Wang2Ying Zhang3Zeming Zhou4Dingsheng Wen5Zhifeng Zhang6Xiaohua Feng7Lu Wen8Jun He9Gang Chen10Guangdong Provincial Key Laboratory of Pharmaceutical Preparations Research and Evaluation, School of Pharmacy & Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, PR ChinaGuangdong Provincial Key Laboratory of Pharmaceutical Preparations Research and Evaluation, School of Pharmacy & Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, PR ChinaGuangdong Provincial Key Laboratory of Pharmaceutical Preparations Research and Evaluation, School of Pharmacy & Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, PR ChinaGuangdong Provincial Key Laboratory of Pharmaceutical Preparations Research and Evaluation, School of Pharmacy & Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, PR ChinaGuangdong Provincial Key Laboratory of Pharmaceutical Preparations Research and Evaluation, School of Pharmacy & Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, PR ChinaGuangdong Provincial Key Laboratory of Pharmaceutical Preparations Research and Evaluation, School of Pharmacy & Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, PR ChinaState Key Laboratory for Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 000853, PR ChinaDepartment of Otolaryngology Head and Neck Surgery, General Hospital of Southern Theater Command of PLA, Guangzhou 510010, PR ChinaGuangdong Provincial Key Laboratory of Pharmaceutical Preparations Research and Evaluation, School of Pharmacy & Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, PR China; Corresponding authors.National Advanced Medical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai 201203, PR China; Corresponding authors.Guangdong Provincial Key Laboratory of Pharmaceutical Preparations Research and Evaluation, School of Pharmacy & Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, PR China; Corresponding authors.Hearing loss, a global health concern, significantly impacts patients with delayed language development, impaired neurocognitive function, and severe social problems. The main cause is the cochlear hair cell damage induced by oxidative stress and inflammation from ototoxic drugs, noise exposure or diabetes. Glycyrrhizic acid (GA), derived from edible herb licorice, is widely utilized in traditional Chinese medicine and clinical treatments for liver diseases. However, its potential in preventing hearing loss remains largely unexplored. Herein, we propose GA as a novel otoprotective agent and demonstrate its capability to prevent hearing loss. Our results show that GA effectively reduces oxidative stress and inflammation induced by cisplatin, aminoglycosides, or even noise and diabetes, thereby protecting cochlear hair cells. In hearing loss models, two commonly used administration methods were compared, with tympanic injection providing better protective effects than oral administration of GA. To enhance oral bioavailability, GA is employed as both the medicine and excipient, and formulated into micelles with curcumin, another extensively used bioactive compound. Interestingly, formulation parameters such as feeding ratio and temperature have little impact on micelle size but significantly affect the drug loading efficiency. The carrier-free strategy can achieve a high drug loading capacity and significantly increase the drug concentration in blood, offering improved preventive efficacy. Notably, the micelles also exhibit protection on kidneys and liver, and do not compromise the antitumor activity of cisplatin. Therefore, GA holds promise as an otoprotective candidate, with potential clinical applications for oral prophylaxis of hearing loss using the micellar formulation.http://www.sciencedirect.com/science/article/pii/S2590156725000258Glycyrrhizic acidCarrier-freeMicelleHearing lossHair cell damage
spellingShingle Huaan Li
Bohan Lin
Shuangwu Wang
Ying Zhang
Zeming Zhou
Dingsheng Wen
Zhifeng Zhang
Xiaohua Feng
Lu Wen
Jun He
Gang Chen
Glycyrrhizic acid and its carrier-free micellar formulation: Unraveling the potential for enhanced oral prevention of hearing loss
International Journal of Pharmaceutics: X
Glycyrrhizic acid
Carrier-free
Micelle
Hearing loss
Hair cell damage
title Glycyrrhizic acid and its carrier-free micellar formulation: Unraveling the potential for enhanced oral prevention of hearing loss
title_full Glycyrrhizic acid and its carrier-free micellar formulation: Unraveling the potential for enhanced oral prevention of hearing loss
title_fullStr Glycyrrhizic acid and its carrier-free micellar formulation: Unraveling the potential for enhanced oral prevention of hearing loss
title_full_unstemmed Glycyrrhizic acid and its carrier-free micellar formulation: Unraveling the potential for enhanced oral prevention of hearing loss
title_short Glycyrrhizic acid and its carrier-free micellar formulation: Unraveling the potential for enhanced oral prevention of hearing loss
title_sort glycyrrhizic acid and its carrier free micellar formulation unraveling the potential for enhanced oral prevention of hearing loss
topic Glycyrrhizic acid
Carrier-free
Micelle
Hearing loss
Hair cell damage
url http://www.sciencedirect.com/science/article/pii/S2590156725000258
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