Localized and sustained release of Botulinum Toxin A from supramolecular peptide hydrogel for strabismus treatment

Botulinum toxin type A (BTXA) is an injectable neurotoxin widely used for the nonsurgical treatment of strabismus. However, its unintended diffusion into non-target extraocular muscles often causes complications such as ptosis and reduces its therapeutic duration. Therefore, suitable delivery platforms to improve both safety and efficacy of BTXA in strabismus treatment are urgently required.

In this research, we co-assembled a pentapeptide hydrogelator Nap-Phe-Phe-Lys-Lys-Lys (NapFFKKK) with BTXA under mild physiological conditions to form a supramolecular hydrogel Gel Nap+BTXA for localized and sustained release of BTXA. The physicochemical characteristics, cytocompatibility, and hemocompatibility of the hydrogel were evaluated in vitro. The in vitro drug release profile and in vivo drug diffusion characteristics were systematically evaluated using single-photon emission computed tomography (SPECT) imaging. After intramuscular injection of Gel Nap+BTXA into the superior rectus muscles of rabbits, the in vivo therapeutic efficacy and biosafety were further verified.

Co-assembly of BTXA with NapFFKKK resulted in the supramolecular hydrogel Gel Nap+BTXA with a well-organized nanofibrous network and enhanced mechanical strength, maintaining the biological activity of BTXA while enabling sustained drug release. In vivo experiments demonstrated that, compared with free BTXA solution, Gel Nap+BTXA showed about 3.1-fold higher local retention of the toxin at 24 h post-injection. Furthermore, Gel Nap+BTXA effectively alleviated ptosis and provided more stable and long-lasting ocular alignment correction up to 2 months, with no detectable ocular or systemic toxicity.

This study demonstrated a safe and efficient localized delivery strategy for BTXA, offering a promising alternative for strabismus treatment.