Scholarlink

Purpose <p>5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent; however, its clinical application is limited by rapid metabolism, short half-life, and systemic toxicity. The present study aimed to develop and optimize 5-FU-loaded nanostructured lipid carriers (5-FU-NLCs) using a Quality-by-Design (QbD) approach to improve formulation performance and achieve sustained drug release.</p> Methods <p>A Quality by Design (QbD) approach employing Box–Behnken design was used to optimize formulation variables, including lipid concentration, surfactant concentration, and homogenization time. 15 experimental runs were generated and evaluated for entrapment efficiency (%EE) and Cumulative drug release (%CDR). The optimized formulation (F3) was characterized using particle size, polydispersity index (PDI), zeta potential, FTIR, DSC, and TEM. In vitro drug release studies were conducted and fitted to kinetic models. In addition, cytotoxicity of the optimized formulation was evaluated against MCF-7 breast cancer cells using the MTT assay. Stability studies were performed for 60 days under refrigerated and room-temperature conditions.</p> Results <p>The optimized formulation (F3) exhibited a particle size of 225.4&#xa0;nm, a PDI of 0.2792, a zeta potential of − 11.37 mV, and an entrapment efficiency of 85.29%. Characterization studies confirmed successful incorporation of 5-FU within the lipid matrix. The formulation demonstrated sustained drug release (~ 80% in 12&#xa0;h), consistent with the Higuchi model (R² = 0.9669). The MTT assay showed concentration-dependent cytotoxicity against MCF-7 cells with an IC₅₀ of 92.57 µM. Stability studies indicated minimal variation in formulation properties.</p> Conclusion <p>The optimized 5-FU-NLC formulation exhibited favorable physicochemical characteristics, sustained-release behavior, and preliminary cytotoxic activity, supporting its potential as a nanoscale drug-delivery platform for further biological investigation.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Formulation and In vitro Evaluation of QbD-Optimized 5-Fluorouracil Nanostructured Lipid Carriers in MCF-7 Cells

  • 期刊论文

  • 发表日期：

    2026年4月21日

查看全文
  • Ashish Singh Chauhan,
  • Pallavi Chand,
  • Sumit Durgapal,
  • Tarun Parashar

摘要

Purpose

5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent; however, its clinical application is limited by rapid metabolism, short half-life, and systemic toxicity. The present study aimed to develop and optimize 5-FU-loaded nanostructured lipid carriers (5-FU-NLCs) using a Quality-by-Design (QbD) approach to improve formulation performance and achieve sustained drug release.

Methods

A Quality by Design (QbD) approach employing Box–Behnken design was used to optimize formulation variables, including lipid concentration, surfactant concentration, and homogenization time. 15 experimental runs were generated and evaluated for entrapment efficiency (%EE) and Cumulative drug release (%CDR). The optimized formulation (F3) was characterized using particle size, polydispersity index (PDI), zeta potential, FTIR, DSC, and TEM. In vitro drug release studies were conducted and fitted to kinetic models. In addition, cytotoxicity of the optimized formulation was evaluated against MCF-7 breast cancer cells using the MTT assay. Stability studies were performed for 60 days under refrigerated and room-temperature conditions.

Results

The optimized formulation (F3) exhibited a particle size of 225.4 nm, a PDI of 0.2792, a zeta potential of − 11.37 mV, and an entrapment efficiency of 85.29%. Characterization studies confirmed successful incorporation of 5-FU within the lipid matrix. The formulation demonstrated sustained drug release (~ 80% in 12 h), consistent with the Higuchi model (R² = 0.9669). The MTT assay showed concentration-dependent cytotoxicity against MCF-7 cells with an IC₅₀ of 92.57 µM. Stability studies indicated minimal variation in formulation properties.

Conclusion

The optimized 5-FU-NLC formulation exhibited favorable physicochemical characteristics, sustained-release behavior, and preliminary cytotoxic activity, supporting its potential as a nanoscale drug-delivery platform for further biological investigation.

Graphical Abstract