Review

Introduction

Botulinum neurotoxins have become essential tools in both therapeutic and aesthetic medicine. Derived from Clostridium botulinum, these neuromodulators inhibit acetylcholine release at neuromuscular junctions, resulting in temporary muscle paralysis. Clinically, this effect is used to reduce the appearance of dynamic wrinkles, particularly in the upper face. Four major botulinum toxin type A formulations are commonly used in aesthetic dermatology: onabotulinumtoxinA (Botox®), abobotulinumtoxinA (Dysport®), incobotulinumtoxinA (Xeomin®), and prabotulinumtoxinA-xvfs (Jeuveau®).

This review explores the molecular differences, pharmacodynamics, diffusion characteristics, immunogenicity, clinical outcomes, and emerging considerations in long-term use of these products.

Mechanism of Action

All botulinum toxin type A formulations function by blocking presynaptic release of acetylcholine via cleavage of SNAP-25, a key SNARE protein required for vesicle docking and neurotransmitter release. This inhibition prevents muscle contraction and leads to temporary denervation. Though each product shares this mechanism, variations in molecular structure and formulation result in different clinical behaviors.

The onset of action typically occurs within 2 to 7 days post-injection, with peak effects at approximately 2 weeks, and duration of action generally lasting 3 to 5 months depending on formulation, dosage, and muscle mass.

Molecular Composition and Formulation Differences

Xeomin® is considered a “naked” neurotoxin as it lacks complexing proteins, which may reduce the risk of immunogenicity. The presence of these accessory proteins in other formulations does not affect clinical efficacy but may influence immune response and product stability.

Diffusion and Spread Characteristics

Diffusion is a critical factor in determining efficacy and potential side effects. Dysport® is thought to have a broader spread due to its lower unit potency and molecular configuration. However, diffusion is not solely dependent on the toxin itself but also on dose, injection technique, muscle anatomy, and dilution practices. New imaging techniques such as electromyography and three-dimensional mapping are being studied to quantify diffusion zones with more precision.

Potency and Dose Conversion

There is no direct unit-to-unit equivalence among neurotoxins:

• Botox:Dysport is often approximated as 1:2.5–3
• Botox:Xeomin is considered 1:1
• Botox:Jeuveau is also considered 1:1 based on current evidence

These conversions are based on clinical studies and are not interchangeable at a molecular level due to proprietary manufacturing processes and potency assays.

Duration and Clinical Efficacy

Clinical duration of effect is influenced by patient metabolism, treatment area, and product used. Meta-analyses have shown comparable efficacy across all four products, though some patients may perceive longer duration or smoother onset with one over another due to formulation characteristics.

A 2019 head-to-head trial (Prager et al.) comparing Botox and Jeuveau found no statistically significant difference in wrinkle reduction outcomes at 30 days post-treatment. Longer-term comparative trials are limited and needed to evaluate sustained efficacy and recurrence timing.

Immunogenicity and Neutralizing Antibodies

One clinical concern is the development of neutralizing antibodies that reduce efficacy. Xeomin®, which lacks complexing proteins, may present a lower immunogenic risk. While the incidence of antibody-mediated resistance is low in aesthetic applications due to infrequent dosing, higher cumulative dose exposure—such as for therapeutic uses or high-frequency cosmetic treatments—may increase immunogenic potential. Studies suggest that minimizing protein load and extending treatment intervals may mitigate risk.

Storage and Handling

• Botox and Xeomin can be stored in a refrigerator before reconstitution.
• Jeuveau and Dysport also require refrigeration but have varied stability profiles post-reconstitution depending on diluent and temperature.
• Studies comparing shelf stability suggest that Xeomin may be more thermally stable due to its formulation without complexing proteins.

Regulatory and Manufacturing Differences

Each neurotoxin is manufactured using proprietary processes, which may affect purity, potency, and immunogenicity. For example:

• Botox is produced by Allergan (AbbVie) in the U.S. using a crystalline preparation.
• Dysport is manufactured by Ipsen in Europe with a lyophilized powder.
• Xeomin is produced by Merz in Germany using chromatographic purification.
• Jeuveau is manufactured by Evolus via Daewoong Pharmaceutical in South Korea using a 900 kDa complex similar to Botox.

These differences, while subtle, contribute to physician preferences and may influence clinical selection based on treatment context and patient response history.

A Note on Clinical Practice

Clinics across North America increasingly personalize neurotoxin selection based on patient goals, previous response, and injection history. For example, providers like Skin Works Medical Spa in El Segundo may offer multiple neurotoxin options in a medically supervised setting, emphasizing safety, precision dosing, and informed decision-making. Though product choice may vary, patient outcomes are consistently tied to injection technique, anatomical understanding, and follow-up care.

Conclusion

Botulinum neurotoxins remain central to non-surgical facial rejuvenation and neurological therapies. Although their mechanisms of action are similar, subtle differences in molecular structure, accessory protein content, diffusion, immunogenicity, and clinical handling may influence choice based on practitioner experience and patient-specific factors. Ongoing comparative research, long-term safety studies, and improved standardization in potency assays are essential to further advancing the science of neuromodulation.

References

• Jankovic, J. et al. (2021). Botulinum Toxin in Clinical Practice. Toxicon, 189, 60–67.
• Prager, W. et al. (2019). A Phase III, Randomized, Double-Blind Study Comparing the Efficacy and Safety of PrabotulinumtoxinA-xvfs and OnabotulinumtoxinA. Dermatologic Surgery.
• Carruthers, A. et al. (2013). A Comparative Review of Botulinum Toxin Formulations. Journal of Cosmetic Dermatology.
• Hexsel, D. et al. (2020). Diffusion, Spread, and Migration of Botulinum Toxin. Clinical, Cosmetic and Investigational Dermatology.
• Dressler, D., & Bigalke, H. (2018). Botulinum Toxin Therapy: A Standardized Approach. Drugs.

Pickett, A. (2020). Manufacturing and Characterization of Botulinum Neurotoxins. Biologics in Therapy.

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