Development of Curcumin-loaded Nanoparticles for Drug Delivery Optimization in the Treatment of Peripheral Nerve Injury

Peripheral nerve injuries (PNI) affect 20 million people, with over 200,00 nerve repairs performed annually in the United States alone. Nerve conduits (NCs) are a commonly employed treatment for injured nerve segments under 3 cm, but unsatisfactory outcomes have been reported for larger gaps. This is in part due to the lack of bioactive agents such as stem cells or growth factors incorporated into FDA-approved NCs. While they have been experimentally shown to promote peripheral nerve regeneration (PNR), their inherent variability, harvesting complexity, and sometimes inadvertently high biological activity pose great regulatory hurdles. Therefore, plant extracts have become an attractive alternative area of bioactive agents proven to improve PNR while overcoming these issues, one of which is curcumin. However, studies largely use unoptimized curcumin which presents an issue as it is hydrophobic and degrades quickly in aqueous solutions. In this study, a nano-formulation comprised of tannic acid and polyvinylpyrrolidone (TA-PVP) was developed to encapsulate curcumin and optimize its delivery to cells. Results show that the developed Cur-TA-PVP nanoparticles (NPs) had an average size of 220 nm, a surface charge of -35mV, and a polydispersity index of 0.3. Further, curcumin was shown to be localized within the core of the NP. This significantly increased the colloidal stability, decreased the degradation rate, and promoted the slow release of curcumin in aqueous solutions. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity of the Cur-TA-PVP NPs was also shown to be superior as compared to free curcumin. Finally, fluorescence microscopy revealed a significantly higher concentration of curcumin in SH-SY5Y, S16 rat Schwann cells, and J774 murine macrophages when delivered via NPs. These results collectively provide evidence for the improved physicochemical properties of the nano-curcumin, which led to improved delivery to cells. Therefore, this formulation has the necessary attributes for incorporation into NCs to promote functional recovery following PNI