Thermal Stability of Botulinum Toxin Type A Formulations Exposed to Heat In Vitro, Assessed by an In Vivo Mouse Potency Bioassay

通过体内小鼠效力生物测定法评估A型肉毒杆菌毒素制剂在体外受热条件下的热稳定性

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Abstract

BACKGROUND: Energy-based devices (EBDs), such as high-intensity focused ultrasound, radiofrequency, and microwave, are increasingly used for facial rejuvenation, raising concerns about whether heat exposure may affect the potency of botulinum toxin. OBJECTIVES: This study investigated the thermal stability of 4 commercial botulinum toxin type A (BoNT/A) products under conditions simulating EBD-related heat exposure, which includes 1 liquid formulation (INNOTOX, Medytox, Seoul, South Korea; hereafter referred to as innoBoNT/A) and 3 powder formulations: onabotulinumtoxinA (onaBoNT/A, BOTOX, Allergan, an Abbvie company, North Chicago, IL), incobotulinumtoxinA (incoBoNT/A, XEOMIN, Merz, Frankfurt, Germany), and abobotulinumtoxinA (aboBoNT/A, DYSPORT, Ipsen, Boulogne-Billancourt, France). METHODS: Mouse intraperitoneal LD(50) potency assays were performed after exposing reconstituted and liquid formulations to 60°C for 10 to 40 min. Relative and normalized potency values were compared before and after exposure. RESULTS: InnoBoNT/A maintained its potency after 25 min of exposure at 60°C, showing no significant loss of biological activity. In contrast, onaBoNT/A, incoBoNT/A, and aboBoNT/A displayed marked reduction in potency under the same conditions. In particular, onaBoNT/A showed a 32% decrease upon exposure at 60°C for 25 min and a complete loss of measurable potency at when exposed at 60°C for 40 min. CONCLUSIONS: Among the BoNT/A formulations evaluated, only the liquid-stabilized preparation preserved potency during thermal stress.

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