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<p>Cancer remains a major global health burden, with conventional therapies limited by systemic toxicity and poor targeting. Hydroxycarbamide (hydroxyurea), an effective antimetabolite used in leukemia, melanoma, and head and neck cancers, is constrained by low solubility, rapid clearance, and dose-limiting toxicity. To address these limitations, this study develops hydroxycarbamide-loaded PLGA nanoparticles using a Quality by Design (QbD) approach to achieve an optimized and reproducible formulation. Critical formulation and process parameters were identified via Fishbone analysis, followed by Taguchi screening and Box–Behnken optimization, resulting in nanoparticles with a particle size of 78.14&#xa0;nm, PDI of 0.207, and zeta potential of − 18.5 mV. These physicochemical attributes enabled efficient drug encapsulation, enhanced solubility, and controlled release. In vitro cytotoxicity studies showed that the nanoparticle formulation was significantly more effective than free hydroxycarbamide, with the IC₅₀ reduced from 0.7 to 0.2&#xa0;µg/mL. This enhanced potency is attributed to improved cellular uptake, drug stabilization, and sustained release from the PLGA matrix, suggesting potential for reduced systemic toxicity. This study presents a robust QbD-driven PLGA nanoparticle platform for hydroxycarbamide delivery with enhanced therapeutic performance. The findings demonstrate its strong translational potential to improve the safety and efficacy of conventional anticancer therapy.</p>

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Quality by Design (QbD)-Assisted Development, Cytotoxicity Profiling, and Pharmacokinetic Assessment of Hydroxycarbamide-Loaded Biodegradable Nanoparticles

  • 期刊论文

  • 发表日期：

    2026年5月27日

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  • Aiswarya Patnaik,
  • Goutam Kumar Jena,
  • Ch Niranjan Patra

摘要

Cancer remains a major global health burden, with conventional therapies limited by systemic toxicity and poor targeting. Hydroxycarbamide (hydroxyurea), an effective antimetabolite used in leukemia, melanoma, and head and neck cancers, is constrained by low solubility, rapid clearance, and dose-limiting toxicity. To address these limitations, this study develops hydroxycarbamide-loaded PLGA nanoparticles using a Quality by Design (QbD) approach to achieve an optimized and reproducible formulation. Critical formulation and process parameters were identified via Fishbone analysis, followed by Taguchi screening and Box–Behnken optimization, resulting in nanoparticles with a particle size of 78.14 nm, PDI of 0.207, and zeta potential of − 18.5 mV. These physicochemical attributes enabled efficient drug encapsulation, enhanced solubility, and controlled release. In vitro cytotoxicity studies showed that the nanoparticle formulation was significantly more effective than free hydroxycarbamide, with the IC₅₀ reduced from 0.7 to 0.2 µg/mL. This enhanced potency is attributed to improved cellular uptake, drug stabilization, and sustained release from the PLGA matrix, suggesting potential for reduced systemic toxicity. This study presents a robust QbD-driven PLGA nanoparticle platform for hydroxycarbamide delivery with enhanced therapeutic performance. The findings demonstrate its strong translational potential to improve the safety and efficacy of conventional anticancer therapy.