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Purpose <p>This study aimed to develop and optimize a PEGylated liposomal dry powder inhaler (LDPI) of Osimertinib Mesylate for targeted pulmonary delivery in non-small cell lung cancer (NSCLC), with the objective of enhancing lung-specific deposition, aerodynamic performance, and sustained drug release while preserving cytotoxic efficacy.</p> Methods <p>PEGylated liposomes were formulated and optimized by modulating formulation and process parameters influencing vesicle size and entrapment efficiency. The optimized 8 mL batch was scaled to 25 mL and lyophilized with trehalose and L-leucine. Liposomes and LDPI powders were characterized for vesicle size, zeta potential, entrapment efficiency, morphology, and powder flow. Particle size distribution was determined using laser diffraction (d50). Aerodynamic performance was assessed using an Anderson cascade impactor. In vitro release, MTT cytotoxicity, and DAPI staining in A549 (RRID: CVCL_0023) cells evaluated sustained release and anticancer activity.</p> Results <p>Optimized liposomes exhibited a size of 158.4 ± 3.41&#xa0;nm, PDI 0.122 ± 0.08, entrapment efficiency 72.68 ± 1.16%, and preserved morphology post-lyophilization. LDPI microparticles showed a median diameter (d50) of 3.56&#xa0;μm and favorable dispersion characteristics. Aerosolization studies yielded an MMAD of 2.89 ± 0.02&#xa0;μm and FPF of 61.65 ± 0.91%, confirming efficient respirable fraction delivery. The LDPI demonstrated sustained release versus burst release from free drug. Cytotoxicity and DAPI assays showed enhanced A549 (RRID: CVCL_0023)cell inhibition and apoptosis.</p> Conclusion <p>The PEGylated liposomal LDPI of Osimertinib Mesylate demonstrates optimal aerodynamic behavior, structural stability, sustained pulmonary release, and improved anticancer efficacy, supporting its promise as a targeted inhalation therapy for NSCLC.</p>

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DoE-Optimized Development of a PEGylated Liposomal Dry Powder Inhaler of Osimertinib Mesylate for Targeted Pulmonary Treatment of Non-Small Cell Lung Cancer

  • 期刊论文

  • 发表日期：

    2026年4月1日

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  • Mansing Patil,
  • Pinkal Patel

摘要

Purpose

This study aimed to develop and optimize a PEGylated liposomal dry powder inhaler (LDPI) of Osimertinib Mesylate for targeted pulmonary delivery in non-small cell lung cancer (NSCLC), with the objective of enhancing lung-specific deposition, aerodynamic performance, and sustained drug release while preserving cytotoxic efficacy.

Methods

PEGylated liposomes were formulated and optimized by modulating formulation and process parameters influencing vesicle size and entrapment efficiency. The optimized 8 mL batch was scaled to 25 mL and lyophilized with trehalose and L-leucine. Liposomes and LDPI powders were characterized for vesicle size, zeta potential, entrapment efficiency, morphology, and powder flow. Particle size distribution was determined using laser diffraction (d50). Aerodynamic performance was assessed using an Anderson cascade impactor. In vitro release, MTT cytotoxicity, and DAPI staining in A549 (RRID: CVCL_0023) cells evaluated sustained release and anticancer activity.

Results

Optimized liposomes exhibited a size of 158.4 ± 3.41 nm, PDI 0.122 ± 0.08, entrapment efficiency 72.68 ± 1.16%, and preserved morphology post-lyophilization. LDPI microparticles showed a median diameter (d50) of 3.56 μm and favorable dispersion characteristics. Aerosolization studies yielded an MMAD of 2.89 ± 0.02 μm and FPF of 61.65 ± 0.91%, confirming efficient respirable fraction delivery. The LDPI demonstrated sustained release versus burst release from free drug. Cytotoxicity and DAPI assays showed enhanced A549 (RRID: CVCL_0023)cell inhibition and apoptosis.

Conclusion

The PEGylated liposomal LDPI of Osimertinib Mesylate demonstrates optimal aerodynamic behavior, structural stability, sustained pulmonary release, and improved anticancer efficacy, supporting its promise as a targeted inhalation therapy for NSCLC.