In silico multiscale comparison of LetibotulinumtoxinA and OnabotulinumtoxinA in glabellar line treatment: diffusion dynamics, receptor affinity, and immunologic clearance

Background Botulinum toxin type A (BoNT-A) is a cornerstone of aesthetic neurotoxin therapy for dynamic facial lines. While OnabotulinumtoxinA (Ona) remains the clinical benchmark, comparative pharmacologic analysis with newer formulations such as LetibotulinumtoxinA (Letibo) remains sparse, particularly under modern high-concentration, low-volume dosing protocols. This study employed multiscale in silico modelling to compare the pharmacokinetic and immunologic profiles of Letibo and Ona, focusing on diffusion behaviour, receptor binding, and immune clearance in glabellar applications. Methods A cohort of 20,000 virtual patients was modelled using finite element meshes derived from high-resolution MRI segmentations of the glabellar region. Tissue anisotropy and poroelasticity were encoded using muscle orientation tensors and permeability matrices. BoNT-A transport was simulated using coupled advection-diffusion-reaction equations, incorporating SV2 receptor binding kinetics and antigenic clearance rates. Epitope docking and HLA class II binding predictions were conducted using homology-modelled BoNT-A structures. Results Letibo demonstrated stronger modelled SV2 binding (ΔG_bind: −11.37 vs. − 11.14 kcal/mol), a consistently smaller effective diffusion radius at lower volumes (up to 20% reduction at 0.045 mL), and more rapid immune clearance (τ_clear = 18.7 h vs. 23.4 h). While HLA epitope exposure profiles were broadly similar, Letibo exhibited slightly reduced surface accessibility under structural equivalence assumptions. Conclusions Letibo may offer pharmacologic advantages in high-precision aesthetic applications due to tighter diffusion and faster receptor engagement. These findings support its use under low-volume protocols but require clinical validation. In silico approaches offer a scientifically grounded framework to evaluate neuromodulator behaviour beyond purity-based marketing claims. Evidence level: Not ratable