<p>Paclitaxel (PTX) is a widely used chemotherapeutic drug, but multiple side effects like systemic toxicity and multidrug resistance are associated with it, which reduce its therapeutic efficiency. Combination therapy is a useful approach to reducing the toxicity of PTX. Curcumin (CUR) is a natural polyphenolic compound with intrinsic photosensitizing properties and can enhance therapeutic efficacy when combined with PTX. In the present study, CUR and PTX were co-encapsulated in PLGA nanoparticles at a drug ratio of 2:1 using the single emulsion solvent evaporation technique. Physicochemical characterization, including UV- vis spectroscopy, FTIR spectroscopy, dynamic light scattering, and polydispersity index of synthesized CUR-PTX NPs, was performed. The in vitro anticancer activity was evaluated against three different cell lines (RD, Hep-2, BT-474), treated with free CUR, free PTX, and CUR-PTX NPs, followed by the irradiation of light to activate the CUR’s photosensitizing effect. Cells were treated with the double concentration of free drugs relative to the drug in NPs, to study the dose-dependent combined effect of drugs. MTT assay of treated cells revealed an improved cytotoxicity of CUR-PTX NPs compared to free drugs. Combinational index analysis also demonstrated a strong synergistic effect between CUR and PTX in NPs. The reactive oxygen species assay was conducted at multiple time points to determine the maximum ROS production contributing to the enhanced cell death. The findings of the present study highlight the potential of CUR-PTX NPs as a synergistic chemo-photodynamic platform for reducing PTX dose-related toxicity and enhancing anti-cancer efficacy.</p> Graphical Abstract <p></p>

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Curcumin-Paclitaxel Co-Loaded PLGA Nanoparticles for Enhanced Anticancer Efficacy via Chemo-Photodynamic Therapy

  • Aleena Zahid,
  • Ahmat Khurshid,
  • Shakeel Ur Rehman

摘要

Paclitaxel (PTX) is a widely used chemotherapeutic drug, but multiple side effects like systemic toxicity and multidrug resistance are associated with it, which reduce its therapeutic efficiency. Combination therapy is a useful approach to reducing the toxicity of PTX. Curcumin (CUR) is a natural polyphenolic compound with intrinsic photosensitizing properties and can enhance therapeutic efficacy when combined with PTX. In the present study, CUR and PTX were co-encapsulated in PLGA nanoparticles at a drug ratio of 2:1 using the single emulsion solvent evaporation technique. Physicochemical characterization, including UV- vis spectroscopy, FTIR spectroscopy, dynamic light scattering, and polydispersity index of synthesized CUR-PTX NPs, was performed. The in vitro anticancer activity was evaluated against three different cell lines (RD, Hep-2, BT-474), treated with free CUR, free PTX, and CUR-PTX NPs, followed by the irradiation of light to activate the CUR’s photosensitizing effect. Cells were treated with the double concentration of free drugs relative to the drug in NPs, to study the dose-dependent combined effect of drugs. MTT assay of treated cells revealed an improved cytotoxicity of CUR-PTX NPs compared to free drugs. Combinational index analysis also demonstrated a strong synergistic effect between CUR and PTX in NPs. The reactive oxygen species assay was conducted at multiple time points to determine the maximum ROS production contributing to the enhanced cell death. The findings of the present study highlight the potential of CUR-PTX NPs as a synergistic chemo-photodynamic platform for reducing PTX dose-related toxicity and enhancing anti-cancer efficacy.

Graphical Abstract