{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T06:36:42Z","timestamp":1793860602624,"version":"4.6.1"},"reference-count":85,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Recent botulinum neurotoxin type A (BoNT\/A) formulations have shifted towards the use of polysorbate 20 (PS20) and polysorbate 80 (PS80) as a non-human-derived excipient to enhance product stability. Polysorbates are a distinct class of synthetic non-ionic surfactants with high heterogeneity in chemical structure and properties. Accumulating mechanistic and clinical evidence suggests that they may trigger immunological reactions, including hypersensitivity and immunogenicity. Such risks are largely associated with their susceptibility to degradation via hydrolysis and oxidation, forming reactive byproducts that can interact with proteins and immune pathways. Despite these mechanistic insights, data on the association between polysorbate excipients and observed immune outcomes in practice is relatively sparse and excipient-related immunogenicity and hypersensitivity is often underrecognized in practice. This review provides a summary of polysorbate excipients in BoNT\/A formulations, focusing on their chemical properties and degradation pathways, characterizing downstream immune effects and appraising available clinical data of polysorbate-containing BoNT\/A formulations. Finally, we discuss potential risk mitigation strategies including process modifications that could prevent degradation, and consideration of alternative excipients, such as human serum albumin, that has been shown to be immunologically inert and has an established safety profile. By integrating chemical, mechanistic, and clinical perspectives, this review seeks to clarify the implications of polysorbate use in BoNT\/A formulations and inform both clinical practice and future formulation strategies.<\/jats:p>","DOI":"10.3390\/toxins17120598","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T15:52:59Z","timestamp":1765813979000},"page":"598","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Immunological Considerations of Polysorbate as an Excipient in Botulinum Neurotoxin Type A Formulations: A Narrative Review"],"prefix":"10.3390","volume":"17","author":[{"given":"Michael Uwe","family":"Martin","sequence":"first","affiliation":[{"name":"Independent Researcher, 31832 Springe, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Frevert","sequence":"additional","affiliation":[{"name":"Merz Pharmaceuticals GmbH, 60318 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Je-Young","family":"Park","sequence":"additional","affiliation":[{"name":"Apkoo-Jung Oracle Dermatology Clinic, Seoul 06022, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Plastic and Cosmetic Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200092, China"},{"name":"Institute of Aesthetic Plastic Surgery and Medicine, Tongji University, Shanghai 200092, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Curry","sequence":"additional","affiliation":[{"name":"Merz Aesthetics, Raleigh, NC 27615, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0882-0508","authenticated-orcid":false,"given":"Wei Qi","family":"Loh","sequence":"additional","affiliation":[{"name":"Merz Asia Pacific Pte. Ltd., Singapore 138589, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sattler, S., Gollomp, S., and Curry, A. (2023). A Narrative Literature Review of the Established Safety of Human Serum Albumin Use as a Stabilizer in Aesthetic Botulinum Toxin Formulations Compared to Alternatives. Toxins, 15.","DOI":"10.3390\/toxins15100619"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kim, J., Kwak, S., Park, M.-S., Rhee, C.-H., Yang, G.-H., Lee, J., Son, W.-C., and Kang, W. (2021). Safety Verification for Polysorbate 20, Pharmaceutical Excipient for Intramuscular Administration, in Sprague-Dawley Rats and New Zealand White Rabbits. 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