Pore Size-Dependent Stereoscopic Hydrogels Enhance the Therapeutic Efficiency of Botulinum Toxin for the Treatment of Nerve-Related Diseases
- Authors
- An, Jeong Man; Shahriar, S.M.Shatil; Lee, Dong Yun; Hwang, Seung Rim; Lee, Yong-Kyu
- Issue Date
- May-2022
- Publisher
- American Chemical Society
- Keywords
- botulinum toxin; carboxymethyl cellulose; hydrogels; nerve diseases; pharmaceuticals
- Citation
- ACS Applied Materials and Interfaces, v.14, no.17, pp.19139 - 191153
- Indexed
- SCIE
SCOPUS
- Journal Title
- ACS Applied Materials and Interfaces
- Volume
- 14
- Number
- 17
- Start Page
- 19139
- End Page
- 191153
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/138784
- DOI
- 10.1021/acsami.2c01738
- ISSN
- 1944-8244
- Abstract
- Botulinum toxin (BoNT) is a major neurotherapeutic protein that has been used at low doses for diverse pharmacological applications. However, the pleiotropic effect of BoNT depends on multiple periodic injections owing to its rapid elimination profile, short-term therapeutic effect, and high mortality rate when administered at high doses. In addition to low patient compliance, these drawbacks represent the significant challenges that limit the further clinical use of BoNT. This study developed a new hydrogel-based single dosage form of BoNT by employing a one-step cross-linking chemistry. Its controlled porous structures and composition facilitated uniform drug distribution inside the hydrogel and controllable release of BoNT mediated by slow diffusion. A single dose remained stable for at least 2.5 months and showed sustained effect for at least 20 weeks, meeting the requirements for a single-dose form of BoNT. Additionally, this dosage form was evaluated as safe from all aspects of toxicology. This delivery system resulted in a 100% survival rate after administering a BoNT dose of 30 units, while a dose of more than 5 units of naked BoNT caused a 100% mortality rate within a few days. Overall, this strategy could provide patients with the first single-dose treatment option of BoNT and improve their quality of life.
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