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<p>The development of scalable and efficient drug delivery systems is crucial to improving the pharmacokinetics and therapeutic performance of poorly soluble bioactive compounds. This study presents the development of solid lipid nanoparticles (SLNs) coated with chitosan (CS) and folate-chitosan (FA-CS) for the delivery of quercetin (Q), a potent phytochemical with significant antioxidant and antitumor properties. A 3<sup>2</sup>-factorial design was employed to optimize crucial formulation parameters, including hydrodynamic diameter (Dh), polydispersity index (PdI), zeta potential (ζ), drug loading (DL), and encapsulation efficiency (EE). Process variables such as sonication time and polymer concentration were systematically evaluated to enhance nanoparticle uniformity and performance. The optimized SLNs achieved mean diameters of 352.8&#xa0;nm (SLN-Q-CS) and 432.3&#xa0;nm (SLN-Q-FA-CS), with high EE (69.7% and 83.8%, respectively). In vitro release studies at pH 5.8 revealed a biphasic release profile characterized by an initial burst (~ 77%) followed by sustained release over 24&#xa0;h. The proposed synthesis approach represents a strategy for enhancing the solubility and controlled release of hydrophobic drugs. Although cancer is a potential application due to folate receptor overexpression in some tumors, further biological studies are required to confirm the therapeutic relevance of the developed system.</p> Graphical Abstract <p></p>

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Design of Experiments of Quercetin-Loaded Solid Lipid Nanoparticles Functionalized with Chitosan and Folic Acid

  • 期刊论文

  • 发表日期：

    2025年10月18日

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  • Júlia Borges de Macedo,
  • Amábile Cristine Woinarovicz,
  • Priscileila Colerato Ferrari

摘要

The development of scalable and efficient drug delivery systems is crucial to improving the pharmacokinetics and therapeutic performance of poorly soluble bioactive compounds. This study presents the development of solid lipid nanoparticles (SLNs) coated with chitosan (CS) and folate-chitosan (FA-CS) for the delivery of quercetin (Q), a potent phytochemical with significant antioxidant and antitumor properties. A 32-factorial design was employed to optimize crucial formulation parameters, including hydrodynamic diameter (Dh), polydispersity index (PdI), zeta potential (ζ), drug loading (DL), and encapsulation efficiency (EE). Process variables such as sonication time and polymer concentration were systematically evaluated to enhance nanoparticle uniformity and performance. The optimized SLNs achieved mean diameters of 352.8 nm (SLN-Q-CS) and 432.3 nm (SLN-Q-FA-CS), with high EE (69.7% and 83.8%, respectively). In vitro release studies at pH 5.8 revealed a biphasic release profile characterized by an initial burst (~ 77%) followed by sustained release over 24 h. The proposed synthesis approach represents a strategy for enhancing the solubility and controlled release of hydrophobic drugs. Although cancer is a potential application due to folate receptor overexpression in some tumors, further biological studies are required to confirm the therapeutic relevance of the developed system.

Graphical Abstract