Pioglitazone/Curcumin co-loaded TPGS-functionalized nanocarriers: an auspicious repurposed therapeutic advance targeting lung and breast carcinoma

This work aims to fabricate D-alpha-tocopheryl polyethylene glycol succinate 1000 (TPGS)-coated bilosomes co-loaded with pioglitazone hydrochloride (PG) and curcumin (CR) to attain a synergistic anticancer activity against the lung and breast cancers cells. PG is a glucose-lowering drug that can disrupt the cancer cell metabolism, while CR is a natural anticancer compound. The bilosomes were first developed and optimized, then coated with TPGS, and finally characterized for their vesicle size (VS), zeta potential (ZP), encapsulation efficiencies (EE), morphological characters, in vitro release patterns, and cytotoxicity and cellular uptake studies on lung (A549) and breast (MCF7) cancer cell lines.

Highlights

• Pioglitazone/curcumin combination nanomedicine unleashes synergistic cytotoxicity on lung and breast carcinoma.
• Pioglitazone and curcumin have been effectively co-loaded into nano-vesicular carrier incorporating sodium deoxycholate and surface modified with TPGS.
• The optimized nano-vesicular carrier demonstrated acceptable physical characteristics and good stability.
• The optimized TPGS- coated nano-vesicular carrier depicted an enhanced cellular uptake and synergistic cytotoxic activity against lung (A549) and breast (MCF7) cancer cells.

The optimized uncoated bilosomes formula demonstrated a VS of 305.5 ± 2.5 nm, ZP of −46.4 ± 1.5 mV, and EE of 85.3 % ± 2.1 and 82.1 % ± 2.3 for CR and PG, respectively, compared to its TPGS-coated-formulation that had a VS of 353.2 ± 3.1 nm, ZP of −55.3 ± 2.5 mV, and EE of 82.4 % ± 2.1 and 80.5 % ± 1.3 for CR and PG, respectively. The optimized TPGS-coated bilosomes encapsulated amorphous drugs without any interactions between them and other formulation excipients. Moreover, it demonstrated a controlled release pattern for both CR and PG and showed 65.5 % ± 2.6 and 60.65 % ± 2.7 release in phosphate-buffer saline (pH 5.5) within 24 h, respectively.

Furthermore, the TPGS coating of bilosomes enhanced their cellular uptake over time and amplified their cytotoxicity as it achieved combination indices of 0.89 and 0.73 on lung and breast cancer cell lines, respectively, compared to the free drugs solution. Accordingly, this study points out a propitious repurposed therapeutic approach of PG/CR combination against lung (A549) and breast (MCF7) cancer cells.

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Materials

Curcumin (CR) (98 %) was obtained from Glentham Life Sciences Ltd, UK. Pioglitazone HCl (PG) (99.98 %) was gifted from Chemi Pharm, Egypt. Sodium Deoxycholate (SDC) was purchased from SD Fine Chemicals, India. Cholesterol (CH), D-alpha-tocopheryl polyethylene glycol succinate-1000 (TPGS), Span® 40, Span® 80 were purchased from Sigma-Aldrish, USA. Dialysis cellulose membrane 12.000–14.000 M.W cut-off was purchased from SERVA Electrophoresis, Heidelberg, Germany. A549 and MCF7 cells were obtained

Shaymaa Elsayed Khater, Riham A. El-Shiekh, Essam Abdel-Sattar, Jihad Mahmoud Alsofany, Pioglitazone/Curcumin co-loaded TPGS-functionalized nanocarriers: an auspicious repurposed therapeutic advance targeting lung and breast carcinoma, International Journal of Pharmaceutics, Volume 682, 2025, 225991, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2025.125991.

See also the video on Vitamin E TPGS below and read more here