Antibody-Integrated Solid-to-Gel Microfilm for Protection Against Botulinum Neurotoxin Type A

TL;DR

A new solid-to-gel microfilm containing antibodies is developed to protect against botulinum neurotoxin type A, offering advantages over traditional liquid formulations.

Contribution

The development of a solid-to-gel microfilm for antibody delivery that enables rapid, stable, and pain-free administration.

Findings

The microfilm dissolves completely within 5 minutes after intradermal insertion.

Mice treated with the microfilm achieved 100% survival in a lethal BoNT/A challenge.

The solid formulation remained stable at ambient temperatures for 3–6 months.

Abstract

Antibodies are indispensable for protection against biological toxins and pathogens, yet their conventional liquid formulations impose severe constraints, including dosing inaccuracy caused by residual fluid remaining in the syringe and limited user convenience such as pain caused by fluid-induced tissue distension and nerve stimulation as well as instability in ambient temperature, and the requirement for low-temperature storage and logistics. These limitations critically impair rapid deployment during golden hour following acute exposure. Here, we report an antibody-integrated solid-to-gel microfilm—demonstrated with a 100 µg anti-BoNT/A dose—jet-printed and low-temperature dried directly onto metal needles for consistent, on-demand use. Upon intradermal insertion, the microfilm fully dissolves within 5 min, driven by hydration-induced swelling of a hyaluronic acid (HA) support layer and rapid release of the antibody. Time-resolved microscopy and UV–vis analysis showed a decrease in residual solid from 2.34 mm3 to 0 over 300 s, with a concomitant rise at 187 nm indicative of complete dissolution. The solid formulation maintained ambient-temperature stability for 3–6 months with pharmacokinetics comparable to conventional subcutaneous liquid injections. In a lethal BoNT/A challenge, treated mice achieved 100% survival for 12 days, whereas controls succumbed within 16 h.

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