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.

Barbara Vigani,Marta Rui,Maria Cristina Bonferoni,Francesca Fagiani,Giuseppina Sandri,Cristina Lanni,Simona Collina,Franca Ferrari,Silvia Rossi

doi:10.3390/md18010021

Barbara Vigani, Marta Rui + Show 7 more

Open Access

https://doi.org/10.3390/md18010021

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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.

Highlights

Spinal cord injury (SCI) is one of the most debilitating pathologies, that results in devastating neurological disabilities; it causes the loss of sensory and motor capabilities, in addition to other common complications, such as cardiac and respiratory dysfunctions, alterations in bladder and bowel control and loss of sexual function [1].The World Health Organization states that, every year, between 250,000 and 500,000 people suffer a SCI worldwide [2]
While the loading of the Sigma 1 Receptor (S1R) agonist should guarantee an attenuation of some secondary injury mechanisms exerting a neuroprotective activity, the scaffold architecture and surface properties and the presence of CS should be responsible for a neuroregenerative effect by supporting axonal outgrowth and sprouting
RC-33: dialysis equilibrium studies demonstrated the formation of an interaction product (IP) between ALG and RC-33 and the capability of such product to control RC-33 release

Summary

Introduction

Spinal cord injury (SCI) is one of the most debilitating pathologies, that results in devastating neurological disabilities; it causes the loss of sensory and motor capabilities, in addition to other common complications, such as cardiac and respiratory dysfunctions, alterations in bladder and bowel control and loss of sexual function [1].The World Health Organization states that, every year, between 250,000 and 500,000 people suffer a SCI worldwide [2]. The majority of SCIs is generally caused by a physical trauma that exerts compression on the spinal cord, triggering, in few minutes, a cascade of cellular, biochemical, and vascular responses; including inflammation, glutamate excitotoxicity, oxidative stress, and mitochondrial dysfunction. Such secondary injury mechanisms are involved in SCI progression, being responsible for an. Mar. Drugs 2020, 18, 21 enlargement of the area of damage; they elicit oligodendrocyte apoptosis and, axon demyelination, leading to the formation of a glial scar, which acts as both a physical and chemical barrier to any further attempts to promote neural repair and functional recovery [3]. The treatments can be classified as neuroprotective or neuroregenerative ones [4,5]

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