Current Strategies in the Development of Nanoformulations to Enhance the Stability of Botox: A Systematic Review.

[PURPOSE] The therapeutic application of Botox is limited due to its inherent structural instability, rapid degradation, and the need for frequent and painful injections. Since nanotechnology-based formulations could provide a solution to these problems, this study systematically investigated the development of stable nanoformulated Botox.

[METHODS] Following PRISMA 2020 guidelines, a systematic search was carried out across PubMed, Web of Science, Scopus, and Google Scholar using both MeSH and non-MeSH keywords, with no date restrictions. Original English-language studies and patents evaluating nanotechnology methods to improve Botox stability in human, animal, or cell models were included. Various nanoformulation approaches, such as high-pressure microfluidization, emulsion and polymer template microfabrication, flash nano-complexation, polyelectrolyte complexation, electrochemical methods, autologous fat emulsification, and reverse-thermal gelation, were examined. Data on synthesis, particle characteristics, buffers/excipients, stability, administration routes, dosing, and efficacy were extracted. Risk of bias was evaluated using both SYRCLE's and Cochrane's RoB 2 tools.

[RESULTS] Nano-Botox exhibited superior stability to heat, pH changes, and enzymatic degradation. Different nanosystems (10-300 nm) and polymeric microparticles (< 100 μm), administered intramuscularly, transdermally, or topically, extended the duration of action from one week to more than 11 months. Silver nanoparticle-based diluents extended refrigerated stability of Botox up to 3-4 months and its clinical efficacy up to > 11 months. Polyethylene glycol derivatives of nano-Botox also revealed promising results.

[CONCLUSION] Nanoformulations with metallic/polymeric nanoparticles and hydrogels greatly increase Botox's stability and its duration of action. In the future, physicochemical properties and safety profiles of these formulations should be optimized for clinical application.