EGF and curcumin co-encapsulated nanoparticle/hydrogel system as potent skin regeneration agent

Abstract

Wound healing is a complex multifactorial process that relies on coordinated signaling molecules to succeed. Epidermal growth factor (EGF) is a mitogenic polypeptide that stimulates wound repair; however, precise control over its application is necessary to reduce the side effects and achieve desired therapeutic benefits. Moreover, the extensive oxidative stress during the wound healing process generally inhibits repair of the injured tissues. Topical applications of antioxidants like curcumin (Cur) could protect tissues from oxidative damage and significantly improve tissue remodeling. To achieve much accelerated wound healing effects, we designed a novel dual drug co-loaded in situ gel-forming nanoparticle/hydrogel system (EGF-Cur-NP/H) which acted not only as a supportive matrix for the regenerative tissue, but also as a sustained drug depot for EGF and Cur. In the established excisional full-thickness wound model, EGF-Cur-NP/H treatment significantly enhanced wound closure through increasing granulation tissue formation, collagen deposition, and angiogenesis, relative to normal saline, nanoparticle/hydrogel (NP/H), Cur-NP/H, and EGF-NP/H treated groups. In conclusion, this study provides a biocompatible in situ gel-forming system for efficient topical application of EGF and Cur in the landscape of tissue repair.

Keywords:

• epidermal growth factor
• EGF
• curcumin
• wound healing
• thermosensitive hydrogel
• nanoparticles

Supplementary materials

Figure S1 ¹H NMR test.

Notes: The ¹H NMR spectrum of 10R5 (A); PLA–10R5–PLA, M_n=4.6×10³ (B); and PLA–10R5–PLA, M_n=19.8×10³ (C).

Abbreviations: ¹H NMR, ¹H nuclear magnetic resonance spectroscopy; PLA, polylactic acid; 10R5, reverse Pluronic^®10R5; M_n, number-average molecular weight.

Figure S2 Analysis of EGF purity by HPLC.

Abbreviations: HPLC, high performance liquid chromatography; EGF, epidermal growth factor.

Figure S3 Particle size distribution of the nanoparticles.

Notes: Particle size distribution of the black NP (A); EGF-NP (B); and Cur-NP (C).

Abbreviations: NP, nanoparticle; Cur, curcumin; EGF, epidermal growth factor.

Figure S4 Rheology analysis of reverse Pluronic^®10R5 aqueous solution (30 wt%) as a function of temperature.

Abbreviations: G′, storage modulus; G″, loss modulus; η, viscosity.

Acknowledgments

This work was financially supported by National Natural Science Foundation of China (31471286), National S&T Major Project (2015ZX09102010), and Sichuan Provincial Science and Technology Department Support Project (2011SZ0222).

Disclosure

The authors report no conflicts of interest in this work.