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Purpose <p>Sorafenib (SFN), a therapeutic agent for hepatocellular carcinoma, belongs to the biopharmaceutics classification system class II. SFN-loaded nanoparticles were formulated using polylactide-co-glycolide (PLGA) for improved solubility and sustained release of SFN. Surface modification using D-α-tocopherol polyethylene glycol succinate 1000 (TPGS) or chitosan (75–85% deacetylated) aims to improve absorption through biomimetic alterations.</p> Methods <p>SPN, SPN with TPGS (SPNT), and SPN with chitosan (SPNC) were prepared as solvent in oil in water emulsions by the solvent evaporation method. The formulations were characterized by in vitro evaluation. Intracellular evaluation was performed by cytotoxicity and uptake. Pharmacokinetic studies were performed by subcutaneous injection in rats.</p> Results <p>The particle sizes of SPN and SPNT were 225.9 ± 2.7&#xa0;nm and 219.4 ± 1.2&#xa0;nm, respectively, with zeta potentials of −&#xa0;10.30&#xa0;mV and −&#xa0;26.49&#xa0;mV. The encapsulation efficiencies were 76.44% for SPN, 77.26% for SPNT, and 69.66% for SPNC. The drug release profile showed rapid release in the cancer tumor environment (pH 5.0–pH 6.8) for 10&#xa0;days for SPN, SPNT, and SPNC. Cytotoxicity and uptake studies supported reduced cell viability and sustainability of intracellular drug delivery. Ex vivo distribution studies showed that SPNT was delivered to the kidney, and SPNC was delivered to the liver. Pharmacokinetic investigations revealed that the subcutaneous injection of the formulated drugs (SPN, SPNT, and SPNC) significantly improved half-life (T<sub>1/2</sub>), increasing by 6.97, 6.11, and 8.56 times, respectively, compared with oral administration of SFN alone.</p> Conclusion <p>The SPNC formulation, demonstrating the highest cancer cell death and prolonged in vivo drug release, was identified as the most suitable treatment formulation.</p>

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Enhanced cellular uptake of sorafenib for hepatocellular carcinoma treatment: surface-modified PLGA nanoparticles with biomimetic alterations

  • 期刊论文

  • 发表日期：

    2025年1月28日

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  • Minki Jin,
  • Jae Hyun Nam,
  • Young-Guk Na,
  • Taek Seon Yun,
  • Bomin Song,
  • Yu-Rim Hwang,
  • Hong-Ki Lee,
  • Jong-Suep Baek,
  • Cheong-Weon Cho

摘要

Purpose

Sorafenib (SFN), a therapeutic agent for hepatocellular carcinoma, belongs to the biopharmaceutics classification system class II. SFN-loaded nanoparticles were formulated using polylactide-co-glycolide (PLGA) for improved solubility and sustained release of SFN. Surface modification using D-α-tocopherol polyethylene glycol succinate 1000 (TPGS) or chitosan (75–85% deacetylated) aims to improve absorption through biomimetic alterations.

Methods

SPN, SPN with TPGS (SPNT), and SPN with chitosan (SPNC) were prepared as solvent in oil in water emulsions by the solvent evaporation method. The formulations were characterized by in vitro evaluation. Intracellular evaluation was performed by cytotoxicity and uptake. Pharmacokinetic studies were performed by subcutaneous injection in rats.

Results

The particle sizes of SPN and SPNT were 225.9 ± 2.7 nm and 219.4 ± 1.2 nm, respectively, with zeta potentials of − 10.30 mV and − 26.49 mV. The encapsulation efficiencies were 76.44% for SPN, 77.26% for SPNT, and 69.66% for SPNC. The drug release profile showed rapid release in the cancer tumor environment (pH 5.0–pH 6.8) for 10 days for SPN, SPNT, and SPNC. Cytotoxicity and uptake studies supported reduced cell viability and sustainability of intracellular drug delivery. Ex vivo distribution studies showed that SPNT was delivered to the kidney, and SPNC was delivered to the liver. Pharmacokinetic investigations revealed that the subcutaneous injection of the formulated drugs (SPN, SPNT, and SPNC) significantly improved half-life (T1/2), increasing by 6.97, 6.11, and 8.56 times, respectively, compared with oral administration of SFN alone.

Conclusion

The SPNC formulation, demonstrating the highest cancer cell death and prolonged in vivo drug release, was identified as the most suitable treatment formulation.