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Purpose <p>Fenofibrate (FN), a Biopharmaceutics Classification System (BCS) class II drug, has poor aqueous solubility and low oral bioavailability. This study aimed to develop polyethylene glycol (PEG)-ylated FN-loaded solid lipid nanoparticles (FN-P-SLNs) to enhance oral bioavailability and lipid-lowering efficacy.</p> Methods <p>FN-P-SLNs were prepared at an optimized ratio of FN/lipid/surfactant/PEG/cryoprotectant (0.5:1.36:1.36:0.07:6.7). Particle size, polydispersity index (PDI), and zeta potential were measured. Physicochemical characteristics were analyzed using FT-IR, DSC, XRD, and SEM. Cytotoxicity was evaluated in Caco-2 cells. In vitro drug release was assessed at different pH conditions. Pharmacokinetic parameters (AUC<sub>t</sub>, C<sub>max</sub>) were compared with raw FN and non-PEGylated FN-SLNs in vivo. Pharmacodynamic effects were evaluated by measuring plasma triglyceride levels in rats.</p> Results <p>FN-P-SLNs showed a mean particle size of 461 ± 240 nm, PDI 0.35 ± 0.15, and zeta potential −50.7 ± 4.5 mV. FT-IR and DSC confirmed successful encapsulation, and XRD indicated a predominantly amorphous state. SEM revealed spherical to oval nanoparticles. Cell viability exceeded 80% at FN concentrations up to 10 μg/mL. Drug release was pH-dependent, reaching 89.6% at pH 4.0 and minimal at pH 1.2. FN-P-SLNs increased AUC<sub>t</sub> by 3.8- and 2.2-fold and C<sub>max</sub> by 5.6- and 4.6-fold, compared with raw FN and non-PEGylated FN-SLNs, respectively. At 48 h, plasma triglyceride levels in the FN-P-SLNs were significantly reduced to 93.7 ± 21.5 mg/dL, while showing similar potency to non-PEGylated FN-SLNs (95.4 ± 34.7 mg/dL).</p> Conclusion <p>PEGylated SLNs significantly improved the oral bioavailability and therapeutic efficacy of FN, demonstrating promise as an oral delivery system for poorly soluble lipid-lowering agents.</p>

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Enhanced oral delivery of fenofibrate using PEGylated solid lipid nanoparticles

  • 期刊论文

  • 发表日期：

    2026年5月21日

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  • Yeong-Eun Choi,
  • Ha Phuong Ngoc Nguyen,
  • Namrah Khan,
  • Jeong-Sook Park

摘要

Purpose

Fenofibrate (FN), a Biopharmaceutics Classification System (BCS) class II drug, has poor aqueous solubility and low oral bioavailability. This study aimed to develop polyethylene glycol (PEG)-ylated FN-loaded solid lipid nanoparticles (FN-P-SLNs) to enhance oral bioavailability and lipid-lowering efficacy.

Methods

FN-P-SLNs were prepared at an optimized ratio of FN/lipid/surfactant/PEG/cryoprotectant (0.5:1.36:1.36:0.07:6.7). Particle size, polydispersity index (PDI), and zeta potential were measured. Physicochemical characteristics were analyzed using FT-IR, DSC, XRD, and SEM. Cytotoxicity was evaluated in Caco-2 cells. In vitro drug release was assessed at different pH conditions. Pharmacokinetic parameters (AUCt, Cmax) were compared with raw FN and non-PEGylated FN-SLNs in vivo. Pharmacodynamic effects were evaluated by measuring plasma triglyceride levels in rats.

Results

FN-P-SLNs showed a mean particle size of 461 ± 240 nm, PDI 0.35 ± 0.15, and zeta potential −50.7 ± 4.5 mV. FT-IR and DSC confirmed successful encapsulation, and XRD indicated a predominantly amorphous state. SEM revealed spherical to oval nanoparticles. Cell viability exceeded 80% at FN concentrations up to 10 μg/mL. Drug release was pH-dependent, reaching 89.6% at pH 4.0 and minimal at pH 1.2. FN-P-SLNs increased AUCt by 3.8- and 2.2-fold and Cmax by 5.6- and 4.6-fold, compared with raw FN and non-PEGylated FN-SLNs, respectively. At 48 h, plasma triglyceride levels in the FN-P-SLNs were significantly reduced to 93.7 ± 21.5 mg/dL, while showing similar potency to non-PEGylated FN-SLNs (95.4 ± 34.7 mg/dL).

Conclusion

PEGylated SLNs significantly improved the oral bioavailability and therapeutic efficacy of FN, demonstrating promise as an oral delivery system for poorly soluble lipid-lowering agents.