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Purpose <p>Alectinib is a BCS Class IV drug with low solubility and permeability. The high dose of ALB (600&#xa0;mg) can lead to several adverse effects, making it necessary to address these issues. This study aims to fabricate a PEGylated ALB-loaded liposome to deliver Alectinib through the pulmonary route to treat non-small cell lung cancer (NSCLC).</p> Methods <p>The PEGylated ALB-loaded liposomes were prepared and optimized using the solvent evaporation method and Box-Behnken design (BBD). A mixture of 0.3% (w/w) phosphatidylcholine, 0.175% (w/w) cholesterol, and 1.25% (w/w) PEG 4000 was dissolved in ethanol. Further, the RP-HPLC method was developed to quantify drugs. The formulation was characterized through various parameters: zeta, size and potential, TEM, SEM, %EE, %CDR, MTT, pharmacokinetics, and toxicity studies.</p> Results <p>PEGylated ALB-loaded liposomes had a particle size of 212.8 ± 1.751&#xa0;nm, a PDI of 0.203 ± 0.034, and an entrapment efficiency of 85%. TEM and SEM images confirmed the morphology of the prepared liposomes. In addition, DSC and FTIR analysis showed drug and excipient compatibility. The drug release was 2.5-fold higher at pH 5.5 and 2.8-fold higher at pH 7.4, compared to drug suspension over 72&#xa0;h. The IC<sub>50</sub> of ALB suspension and PEGylated ALB-loaded liposome were 2.55 ± 0.045 µM and 1.029 ± 0.0251 µM, respectively, by the A549 human lung cell line study. The ex vivo CLSM study showed that ALB penetrated deeper in lung tissue. The pharmacokinetic study showed that ALB from liposomes had higher T<sub>1/2</sub> (1.77 times) and AUC0-t (1.52 times) than ALB suspension in C57BL/6 mice. No significant changes were observed in the biochemical estimations or acute toxicity studies. Additionally, no notable changes were detected during the 6-month stability study.</p> Discussion and Conclusion <p>PEGylated ALB-loaded liposomes showed better drug release, improved cellular uptake, superior pharmacokinetics, good biocompatibility, and stability, showing their promise as an effective inhalational delivery system for ALB in treating NSCLC. Therefore, PEGylated liposomes appear to be a promising carrier for the inhalational delivery of ALB for NSCLC.</p> Graphical Abstract <p></p>

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PEGylated Liposomal Formulation of Alectinib Against Non-Small Cell Lung Cancer: Optimization, Characterization, Stability Assessment, In Vitro Cytotoxicity in A549 Cells and in Vivo Efficacy in C57BL/6 Mice

  • 期刊论文

  • 发表日期：

    2025年9月26日

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  • Saeem Ahmad,
  • Shahnaj Bano,
  • Nasr A. Emad,
  • Iqra Zai,
  • Shadab Alam,
  • Mohd Aqil,
  • Yasmin Sultana

摘要

Purpose

Alectinib is a BCS Class IV drug with low solubility and permeability. The high dose of ALB (600 mg) can lead to several adverse effects, making it necessary to address these issues. This study aims to fabricate a PEGylated ALB-loaded liposome to deliver Alectinib through the pulmonary route to treat non-small cell lung cancer (NSCLC).

Methods

The PEGylated ALB-loaded liposomes were prepared and optimized using the solvent evaporation method and Box-Behnken design (BBD). A mixture of 0.3% (w/w) phosphatidylcholine, 0.175% (w/w) cholesterol, and 1.25% (w/w) PEG 4000 was dissolved in ethanol. Further, the RP-HPLC method was developed to quantify drugs. The formulation was characterized through various parameters: zeta, size and potential, TEM, SEM, %EE, %CDR, MTT, pharmacokinetics, and toxicity studies.

Results

PEGylated ALB-loaded liposomes had a particle size of 212.8 ± 1.751 nm, a PDI of 0.203 ± 0.034, and an entrapment efficiency of 85%. TEM and SEM images confirmed the morphology of the prepared liposomes. In addition, DSC and FTIR analysis showed drug and excipient compatibility. The drug release was 2.5-fold higher at pH 5.5 and 2.8-fold higher at pH 7.4, compared to drug suspension over 72 h. The IC50 of ALB suspension and PEGylated ALB-loaded liposome were 2.55 ± 0.045 µM and 1.029 ± 0.0251 µM, respectively, by the A549 human lung cell line study. The ex vivo CLSM study showed that ALB penetrated deeper in lung tissue. The pharmacokinetic study showed that ALB from liposomes had higher T1/2 (1.77 times) and AUC0-t (1.52 times) than ALB suspension in C57BL/6 mice. No significant changes were observed in the biochemical estimations or acute toxicity studies. Additionally, no notable changes were detected during the 6-month stability study.

Discussion and Conclusion

PEGylated ALB-loaded liposomes showed better drug release, improved cellular uptake, superior pharmacokinetics, good biocompatibility, and stability, showing their promise as an effective inhalational delivery system for ALB in treating NSCLC. Therefore, PEGylated liposomes appear to be a promising carrier for the inhalational delivery of ALB for NSCLC.

Graphical Abstract