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. 2024 May 12;29(10):2281.
doi: 10.3390/molecules29102281.

Design and Development of a Polymeric-Based Curcumin Nanoparticle for Drug Delivery Enhancement and Potential Incorporation into Nerve Conduits

Giuliana Gan Giannelli  1   2 , Edwin Davidson  1   3 , Jorge Pereira  1   3 , Swadeshmukul Santra  1   2   3
Affiliations

Design and Development of a Polymeric-Based Curcumin Nanoparticle for Drug Delivery Enhancement and Potential Incorporation into Nerve Conduits

Giuliana Gan Giannelli et al. Molecules. .

Abstract

Peripheral nerve injuries (PNI) impact millions of individuals in the United States, prompting thousands of nerve repair procedures annually. Nerve conduits (NC) are commonly utilized to treat nerve injuries under 3 cm but larger gaps still pose a challenge for successful peripheral nerve regeneration (PNR) and functional recovery. This is partly attributed to the absence of bioactive agents such as stem cells or growth factors in FDA-approved conduits due to safety, harvesting, and reproducibility concerns. Therefore, curcumin, a bioactive phytochemical, has emerged as a promising alternative bioactive agent due to its ability to enhance PNR and overcome said challenges. However, its hydrophobicity and rapid degradation in aqueous solutions are considerable limitations. In this work, a nanoscale delivery platform with tannic acid (TA) and polyvinylpyrrolidone (PVP) was developed to encapsulate curcumin for increased colloidal and chemical stability. The curcumin nanoparticles (CurNPs) demonstrate significantly improved stability in water, reduced degradation rates, and controlled release kinetics when compared to free curcumin. Further, cell studies show that the CurNP is biocompatible when introduced to neuronal cells (SH-SY5Y), rat Schwann cells (RSC-S16), and murine macrophages (J774 A.1) at 5 μM, 5 μM, and 10 μM of curcumin, respectively. As a result of these improved physicochemical properties, confocal fluorescence microscopy revealed superior delivery of curcumin into these cells when in the form of CurNPs compared to its free form. A hydrogen peroxide-based oxidative stress study also demonstrated the CurNP's potential to protect J774 A.1 cells against excessive oxidative stress. Overall, this study provides evidence for the suitability of CurNPs to be used as a bioactive agent in NC applications.

Keywords: curcumin nanoparticles; nanodelivery; nerve conduits; oxidative stress; peripheral nerve regeneration; polyvinylpyrrolidone; tannic acid.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
(A) SEM image demonstrates somewhat spherical CurNPs with some agglomeration. (B) DLS histogram demonstrates the hydrodynamic diameter (size) distribution of CurNPs, with notable polydispersity due to the agglomeration of primary particles. (C) Zeta potential charge distribution of CurNPs in an aqueous solution.
Figure 2
Figure 2
(A) UV–Visible spectra of curcumin, CurNP, and TA–PVP to confirm the presence of components within the NP system. (B) FTIR spectra of curcumin, CurNP, and TA–PVP to confirm the presence and interactions of components within the NP system. (C) Fluorescence emission spectra of CurNP and curcumin in an aqueous solution to determine localization of curcumin within the NP.
Figure 3
Figure 3
(A) Degradation rate measured through the absorbance of curcumin and CurNPs in PBS at 425 nm for 24 h. Statistical analysis was performed using simple liner regression (p < 0.0001). (B) Cumulative release of curcumin from CurNPs dispersed in water, measured up to 30 h.
Figure 4
Figure 4
Viability of J774A.1, SH-SY5Y, RSC-S16 cells upon treatment with curcumin, CurNPs, and TA–PVP for 24 h, followed by AlamarBlue reagent for 2 h. Fluorescence was measured at Ex/Em 560/590 nm. Error bars correspond to a standard deviation (n = 9).
Figure 5
Figure 5
Confocal fluorescence microscopy images of (A) SH-SY5Y, (C) J774A.1, and (E) RSC-S16 upon treatment with CurNPs for 24 h (green channel). Images (B) SH-SY5Y, (D) J774A.1, and (F) RSC-S16 correspond to cells treated with free curcumin for 24 h. (G–I) Quantitative analysis of green fluorescence intensity in for SH-SY5Y, J774A.1, RSC-S16 cells, respectively (normalized). The red scale bar represents 20 µm. The bar graphs represent the mean and error bars correspond to the standard deviation (n = 3). Statistical analysis was performed using one-way ANOVA (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001, ns not significant).
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