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

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

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.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Curcumin* / chemistry
  • Curcumin* / pharmacokinetics
  • Curcumin* / pharmacology
  • Drug Liberation
  • Female
  • HeLa Cells
  • Humans
  • Liposomes* / chemistry
  • Liposomes* / pharmacokinetics
  • Mice
  • Mice, Inbred BALB C
  • Particle Size
  • Rats, Sprague-Dawley
  • Uterine Cervical Neoplasms* / drug therapy
  • Uterine Cervical Neoplasms* / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Liposomes
  • Curcumin
  • Antineoplastic Agents

Grants and funding

This study was supported by the National Natural Science Foundation project of China (No. 82474105), Sichuan Natural Science Foundation Project (No. 2024NSFSC0049, 2024NSFSC0625), Sichuan Science and Technology Program (No. 2022YFS0630, 2022YFS0619), the Key R&D Project of Luzhou-Southwest Medical University (No. 2023LZXNYDHZ002), the Cooperation Projects of Sichuan Credit Pharmaceutical CO., Ltd., Central Nervous System Drug Key Laboratory of Sichuan Province (No. 210027-01SZ, 200017-01SZ, 230007-01SZ, 230008-01SZ), the Chongqing Traditional Chinese Medicine Inheritance and Innovation Team Construction Project “Traditional Chinese Medicine New Drug and Safety Research Inheritance and Innovation Team” (No. 2022-8). Luzhou Science and Technology Plan Project (No. 2023JYJ034, 2023JYJ022, 2022-SYF-85).