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. 2024 Dec 13:19:13411-13428.
doi: 10.2147/IJN.S493074. eCollection 2024.

Development of the Curcumin Analog CA7 Liposome and Its Evaluation for Efficacy Against Cervical Cancer in vitro and in vivo

Linjin Xiong #  1   2   3   4 , Yumeng Wei #  1   3 , Hui Si #  4 , Zheng Li  1   2   3 , Jie Wen  1   2   3 , Furong Liu  5 , Xiaodong Wang  6 , Hongru Yang  7 , Ligang Chen  8 , Chao Pi  1   3 , Yunwei Han  7 , Ling Zhao  2   3   4
Affiliations

Development of the Curcumin Analog CA7 Liposome and Its Evaluation for Efficacy Against Cervical Cancer in vitro and in vivo

Linjin Xiong et al. Int J Nanomedicine. .

Abstract

Objective: The objective of this study was to develop liposomes (LP) containing a curcumin (CU) analog CA7 to enhance its pharmacokinetic profile and anti-cervical cancer (CC) effects.

Methods: Single-factor and Box-Behnken experiments were conducted to optimize the formulation of CA7-loaded liposomes (CA7-LP). The in vitro release, stability, biocompatibility, and pharmacokinetic of CA7-LP were evaluated. The biological effects of CA7-LP on Hela cells were assessed using MTT assays, colony formation assays, wound healing assays, and flow cytometry. Additionally, the anti-CC efficacy of CA7-LP was tested in mouse models of transplanted tumors.

Results: The optimal formulation of CA7-LP exhibited a particle size of 92.43 ± 1.52 nm, a polydispersity index of 0.27 ± 0.01, an encapsulation efficiency of 97.79 ± 1.49%, a drug loading of 3.23 ± 0.20%, and a zeta potential of -6.69 ± 0.77 mV. Transmission electron microscopy confirmed that a spherical morphology was exhibited by CA7-LP. The cumulative in vitro release of CA7-LP was found to be 2.84 times greater than that of CA7, and stability at room temperature was maintained for at least 90 d. Furthermore, a significantly higher uptake of CA7-LP by Hela cells was observed compared to curcumin and CA7, leading to enhanced inhibition of cell proliferation, migration and cell cycle, as well as increased apoptosis (p < 0.05). In vivo studies revealed that CA7-LP exhibited superior pharmacokinetic properties compared to CA7 (AUC: 3.58-fold, Cmax: 5.65-fold, t1/2z: 1.2-fold). The anti-CC effects of CA7-LP were found to be comparable to those of Cisplatin injection, with a better safety profile.

Conclusion: The newly developed CA7-LP is considered a promising candidate for the treatment of CC, demonstrating high potential for clinical application.

Keywords: cervical cancer; curcumin analog CA7; hela; liposome.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

None
Graphical abstract
Figure 1
Figure 1
Chemical structure of CU (A) and CA7 (B).
Figure 2
Figure 2
(A) The effects of ultrasound intensity, ultrasound time, CA7 dosage, lecithin dosage, and cholesterol dosage on PS, PDI, and EE of CA7-LP. (B) The effects of lyophilized protectants on PS and PDI of CA7-LP. (C) Two-way interaction contour plots of three factors. (D) PS distribution of CA7-LP. (E) Morphology of CA7-LP by transmission electron microscopy.
Figure 3
Figure 3
The uptake of CA7-LP by Hela cells.
Figure 4
Figure 4
Inhibition of Hela cell activity by CA7-LP. (A) The effects of CU, CA7, CA7-LP, and DDP-INJ on Hela cell activity; *p < 0.05 vs CA7; #p < 0.05 vs DDP-INJ. (B) The IC50 of CU, CA7, CA7-LP, and DDP-INJ inhibits Hela cell activity. The green color indicates lower toxicity of the drug on Hela cells at the specified time point, while the red color reflects higher toxicity. (C and D) The effects of CU, CA7, CA7-LP, and DDP-INJ on the proliferation of Hela cells, *p < 0.05. (E and F) The effects of CU, CA7, CA7-LP, and DDP-INJ on the migration of Hela cells, *p < 0.05.
Figure 5
Figure 5
CA7-LP suppressed Hela cells by preventing cell cycle progression and triggering apoptosis. (A and B) The effects of CU, CA7, CA7-LP, and DDP-INJ on apoptosis induction, *p < 0.05. (C and D) The effects of CU, CA7, CA7-LP, and DDP-INJ on the cell cycle of Hela, *p < 0.05 vs Control.
Figure 6
Figure 6
CA7-LP has good stability, release characteristics and biocompatibility. (A) Stability of CA7-LP suspension at 25°C, *p < 0.05. (B) Stability of CA7-LP suspension at 4°C. (C) Stability of CA7-LP lyophilized powder at 25°C for 90 d. (D) Release curves of CA7-LP in vitro. (E and F) Biocompatibility Evaluation of CA7-LP.
Figure 7
Figure 7
The concentration curves of CA7 and CA7-LP.
Figure 8
Figure 8
CA7-LP demonstrated favorable anti-CC effects in vivo. (A) The curves of tumor volume (n = 5). (B) The curves of nude mouse body weight (n = 5). (C) Transplanted tumor in nude mice. (D) Tumor weight histogram, *p < 0.05. (E) Immunohistochemical staining of tumors. (F) H&E staining of tumors. (G) H&E staining of heart, liver, lung and kidney in nude mice.
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