Pore Size-Dependent Stereoscopic Hydrogels Enhance the Therapeutic Efficiency of Botulinum Toxin for the Treatment of Nerve-Related Diseases

Abstract

Botulinum toxin (BoNT) is a major neurotherapeutic protein that has been used at low doses for diverse pharmacological applications. However, the pleiotropic effect of BoNT depends on multiple periodic injections owing to its rapid elimination profile, short-term therapeutic effect, and high mortality rate when administered at high doses. In addition to low patient compliance, these drawbacks represent the significant challenges that limit the further clinical use of BoNT. This study developed a new hydrogel-based single dosage form of BoNT by employing a one-step cross-linking chemistry. Its controlled porous structures and composition facilitated uniform drug distribution inside the hydrogel and controllable release of BoNT mediated by slow diffusion. A single dose remained stable for at least 2.5 months and showed sustained effect for at least 20 weeks, meeting the requirements for a single-dose form of BoNT. Additionally, this dosage form was evaluated as safe from all aspects of toxicology. This delivery system resulted in a 100% survival rate after administering a BoNT dose of 30 units, while a dose of more than 5 units of naked BoNT caused a 100% mortality rate within a few days. Overall, this strategy could provide patients with the first single-dose treatment option of BoNT and improve their quality of life.

Transforming layered 2D mats into multiphasic 3D nanofiber scaffolds with tailored gradient features for tissue regeneration

“…Overall, for both biphasic and multiphasic scaffolds, the gap distances, volume, and porosity were consistently larger in the aligned portion compared to the random portion, while the normalized densities displayed the opposite trend (Figure S4a-d). These techniques provide a straightforward means to control the porosity of multiphasic scaffolds without the need for crosslinkers, [17] solvents, [18] surfactants, [3] template agents, [19] catalysts, [20] or cryoprotectant. [21] Furthermore, multiphasic scaffolds featuring dual gradients in gap distance and fiber organization hold significant potential for emulating the intricate structure of the ECM and modulating cellular behavior.…”

Carbon Nanotube and Its Derived Nanomaterials Based High Performance Biosensing Platform

“…In addition, it is very important to determine the toxicity of carbon nanotubes for clinical use because there is a possibility of accumulation in organs [ 90 ]. Like many studies conducted for clinical application, CNTs also need to be carefully evaluated and verified for toxicity in vitro and in vivo [ 91 , 92 ]. Here, we provide the toxicity of carbon nanotubes and present methodological explanations to reduce toxicity.…”