Dual-functioning scaffolds for the treatment of spinal cord injury: Alginate nanofibers loaded with the sigma 1 receptor (S1R) Agonist RC-33 in chitosan films

Vigani, B., Rossi, S., Sandri, G., Bonferoni, M.C., Rui, M., Collina, S., Fagiani, F., Lanni, C., Ferrari, F.

Mar. Drugs 2020, 18(1), 21; https://doi.org/10.3390/md18010021

ABSTRACT. The present work proposed a novel therapeutic platform with both neuroprotective and neuroregenerative potential to be used in the treatment of spinal cord injury (SCI). A dual-functioning scaffold for the delivery of the neuroprotective S1R agonist, RC-33, to be locally implanted at the site of SCI, was developed. RC-33-loaded fibers, containing alginate (ALG) and a mixture of two different grades of poly(ethylene oxide) (PEO), were prepared by electrospinning. After ionotropic cross-linking, fibers were incorporated in chitosan (CS) films to obtain a drug delivery system more flexible, easier to handle, and characterized by a controlled degradation rate. Dialysis equilibrium studies demonstrated that ALG was able to form an interaction product with the cationic RC-33 and to control RC-33 release in the physiological medium. Fibers loaded with RC-33 at the concentration corresponding to 10% of ALG maximum binding capacity were incorporated in films based on CS at two different molecular weights-low (CSL) and medium (CSM)-solubilized in acetic (AA) or glutamic (GA) acid. CSL- based scaffolds were subjected to a degradation test in order to investigate if the different CSL salification could affect the film behavior when in contact with media that mimic SCI environment. CSL AA exhibited a slower biodegradation and a good compatibility towards human neuroblastoma cell line. © 2019 by the authors.