Development of alginate-spermidine micro/nanogels as potential antioxidant and anti-inflammatory tool in peripheral nerve injuries. Formulation studies and physico-chemical characterization.

The development of a successful strategy to ensure a full recovery in patients affected by peripheral nerve injury (PNI), one of the most debilitating pathologies, is, still today, a major clinical challenge. Herein, spermidine (SP), an endogenous polyamine, is employed with a dual role: as cross-linking agent for alginate (ALG) and as antioxidant and anti-inflammatory compound. In particular, micro/nanogels based on the ionic interaction between ALG and SP were obtained via ionotropic gelation. Different ALG concentrations and viscosity grades and different SP concentrations were considered. The influence of such variables on micro/nanogels size was investigated by means of a Design of Experiments (DoE) approach (full factorial design). The formation of micro/nanogels was proved by Scanning Electron Microscope (SEM) analysis and by rheological and profilometry measurements. Fourier Transform Infrared (FTIR) measurements performed on nanogels of optimal composition confirmed SP-ALG interaction. The addition of trehalose as cryoprotectant agent to nanogel dispersion was considered in view of the employment of freeze-drying process to obtain a stable product. Moreover, in vitro studies on Schwann cells proved the ability of SP of expressing antioxidant and anti-inflammatory properties, even if involved in the formation of nanogels.

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.