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<p>The development of biopolymer-based nanogels offers a promising strategy to improve the therapeutic efficacy and safety of conventional chemotherapeutics. In this study, pectin was employed as a dual-function agent, acting as both a stabilizer and a reducing agent, to fabricate silver-incorporated nanogel (Pec-Ag-Ngel) for the delivery of 5-fluorouracil (5-FU). Structural and physicochemical analyses confirmed successful nanogel formation, with FTIR indicating pectin’s hydroxyl and carboxyl groups coordinated to silver, XRD showing crystalline silver peaks, and EDAX verifying elemental silver alongside pectin-derived carbon and oxygen. SEM images revealed a porous nanoscale morphology, suggesting high-surface area suitable for drug-encapsulation and controlled release. The nanogels exhibited high drug encapsulation efficiency (80.09 ± 2.58%) and sustained release behavior under physiological and acidic pH, indicating their potential for controlled delivery. The MTT assay on HepG2 cells revealed a dose- and time-dependent cytotoxic effect of 5-FU and Pec-Ag-Ngel. The nanogel exhibited a comparatively higher IC₅₀ value (IC₅₀ = 0.9354&#xa0;µg/mL) than free 5-FU (IC₅₀ = 0.3568&#xa0;µg/ml), indicating a sustained and controlled drug release with reduced immediate toxicity. Acute toxicity studies further highlighted the improved safety profile of the nanogel formulation. While pure 5-FU showed an LD₅₀ cut-off value in the range of 50–300&#xa0;mg/kg, encapsulated 5-FU within Pec-Ngel demonstrated a higher LD₅₀ range of 300–500&#xa0;mg/kg, with survival at lower doses and controlled mortality only at extremely high concentrations. Overall, the findings highlight Pec-Ag-Ngel as a green, safe, and effective platform that mitigates 5-FU toxicity and holds strong potential for next-generation anticancer drug delivery.</p>

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pH-Responsive Pectin–Silver Nanogel for 5-Fluorouracil Delivery to HepG2 cells: Formulation, Characterization and Acute Oral Toxicity Evaluation

  • 期刊论文

  • 发表日期：

    2026年1月16日

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  • Vaishnavi Shashidhara,
  • Arvind H. Jadhav,
  • Kavina Ganapathy,
  • Madhavarani Alwarsamy

摘要

The development of biopolymer-based nanogels offers a promising strategy to improve the therapeutic efficacy and safety of conventional chemotherapeutics. In this study, pectin was employed as a dual-function agent, acting as both a stabilizer and a reducing agent, to fabricate silver-incorporated nanogel (Pec-Ag-Ngel) for the delivery of 5-fluorouracil (5-FU). Structural and physicochemical analyses confirmed successful nanogel formation, with FTIR indicating pectin’s hydroxyl and carboxyl groups coordinated to silver, XRD showing crystalline silver peaks, and EDAX verifying elemental silver alongside pectin-derived carbon and oxygen. SEM images revealed a porous nanoscale morphology, suggesting high-surface area suitable for drug-encapsulation and controlled release. The nanogels exhibited high drug encapsulation efficiency (80.09 ± 2.58%) and sustained release behavior under physiological and acidic pH, indicating their potential for controlled delivery. The MTT assay on HepG2 cells revealed a dose- and time-dependent cytotoxic effect of 5-FU and Pec-Ag-Ngel. The nanogel exhibited a comparatively higher IC₅₀ value (IC₅₀ = 0.9354 µg/mL) than free 5-FU (IC₅₀ = 0.3568 µg/ml), indicating a sustained and controlled drug release with reduced immediate toxicity. Acute toxicity studies further highlighted the improved safety profile of the nanogel formulation. While pure 5-FU showed an LD₅₀ cut-off value in the range of 50–300 mg/kg, encapsulated 5-FU within Pec-Ngel demonstrated a higher LD₅₀ range of 300–500 mg/kg, with survival at lower doses and controlled mortality only at extremely high concentrations. Overall, the findings highlight Pec-Ag-Ngel as a green, safe, and effective platform that mitigates 5-FU toxicity and holds strong potential for next-generation anticancer drug delivery.