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. 2025 Jan;24(1):e16573.
doi: 10.1111/jocd.16573. Epub 2024 Sep 23.

Development of a Simvastatin-Loaded Copolymer Acid-Sensitive Nanocarrier and Its Experimental Use in the Treatment of Keloids

Bin-Yu Zhuang  1 , Fang-Chi Hu  2 , Xuan Gao  3 , Qi Leng  4 , Ying Zhang  5 , Yan You  1
Affiliations

Development of a Simvastatin-Loaded Copolymer Acid-Sensitive Nanocarrier and Its Experimental Use in the Treatment of Keloids

Bin-Yu Zhuang et al. J Cosmet Dermatol. 2025 Jan.

Abstract

Objective: The lipid-lowering simvastatin (SIM) has been shown to be an effective inhibitor of keloid proliferation. However, due to its low water solubility and short half-life, simvastatin aggregates to the liver and does not reach the skin lesions after oral administration, which restricts its widespread clinical use. The development of nanomedicine provides the possibility for us to break through this bottleneck problem clinically. The objective of this study was to investigate the feasibility of using complex nanocontrolled delivery system (CNDS), simvastatin-loaded polyethylene glycol-poly lactic-co-glycolic acid (PEG-PLGA), in the treatment of keloids.

Methods: In the in vitro study, the release of simvastatin in fibroblasts by CNDS@Simvastatin and its effect on inhibition of the proliferation of fibroblasts, Col Ι, and CTGF by the slow release of simvastatin were assessed. The efficacy of CNDS@Simvastatin in improving keloids and the biocompatibility and safety of CNDS@Simvastatin were examined in vivo by establishing a murine ear keloid model.

Results: CNDS@Simvastatin showed sustained and uniform inhibition of the proliferation of fibroblasts, Col Ι, and CTGF via the gradual release of simvastatin over 72 h. It was efficient in the treatment of the murine ear keloid with no observable toxic side effects on various organs.

Conclusion: Simvastatin-loaded copolymer acid-sensitive nanocarriers, CNDS@Simvastatin nanospheres, were successfully developed in this study, and these were characterized by favorable physicochemical properties and biocompatibility.

Keywords: PEG; PH; PLGA; complex nanocontrolled delivery system; fibroblasts; keloid; simvastatin.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Schematic diagram of drug release after CNDS@Simvastatin enters fibroblasts.
FIGURE 2
FIGURE 2
(A) Transmission electron microscopy of CNDS@Simvastatin; (B) Particle size distribution of CNDS; (C) Particle size distribution of CNDS@Simvastatin.
FIGURE 3
FIGURE 3
Drug release curves of simvastatin released from CNDS@Simvastatin in different pH solutions.
FIGURE 4
FIGURE 4
Cytotoxicity test of each group.
FIGURE 5
FIGURE 5
(A–C) Immunofluorescence staining using proliferating cell nuclear antigen (PCNA) antibody to observe the cell growth and proliferation of each group performed at 24 h (A); 48 h (B); and 72 h (C) using confocal microscopy; and (D) Drug release after CNDS@Simvastatin entered fibroblasts at 24, 48, and 72 h.
FIGURE 6
FIGURE 6
Collagen I and CTGF mRNA, protein, and fibroblast viability expression levels detected using Q‐PCR, Western blot, and CCK8 at 24, 48, and 72 h in the four groups. (A) MRNA expression level of Collagen I; (B) MRNA expression level of CTGF; (C) Collagen I protein expression level; (D) CTGF protein expression level; (E) Fibroblast viability expression level. *p < 0.05, **p < 0.01, ***p < 0.001.
FIGURE 7
FIGURE 7
(A) Expression levels of apoptosis in fibrocytes of the four groups detected using flow cytometry. (B) Statistical data of apoptosis detected using flow cytometry. *p < 0.05, **p < 0.01, ***p < 0.001.
FIGURE 8
FIGURE 8
(A) Therapeutic evaluation of keloid animal models in the mice ears of each group; (B) HE staining of heart, liver, and kidney organs in mice after keloid treatment in the ears of each group.
See this image and copyright information in PMC

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