Inhalable microspheres embedding chitosan-coated PLGA nanoparticles for 2-methoxyestradiol

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pharmacology

Background:

• Developing effective lung-targeted drug delivery is crucial for lung cancer treatment.
• Local delivery systems aim to improve therapeutic efficacy and reduce systemic side effects.
• Microspheres (MS) offer a potential matrix for encapsulating nanoparticles for pulmonary administration.

Purpose of the Study:

• To design and evaluate novel respirable microspheres (MS) embedding chitosan-coated nanoparticles (CNP-MS) for targeted lung delivery of 2-methoxyestradiol (2-ME).
• To assess the enhanced cytotoxicity and pulmonary safety profile of the developed 2-ME CNP-MS.
• To investigate the potential of CNP-MS as an inhalation agent for lung cancer therapy.

Main Methods:

• 2-methoxyestradiol (2-ME) loaded chitosan-coated poly(d,l-lactide-co-glycolide) nanoparticles (CNP-MS) were prepared using spray-drying.
• Characterization included morphology, redispersability, fine particle fraction (FPF), and drug release studies.
• Cytotoxicity assays, lung deposition studies, and histological examinations were performed.

Main Results:

• The 2-ME CNP-MS exhibited spherical morphology, good redispersability, high respirable fraction, and sustained drug release.
• CNP-MS significantly enhanced the cytotoxicity of 2-ME against SPC-A1 cells (8.8-fold vs. solution, 3.65-fold vs. NP).
• Pulmonary administration in rats showed good lung distribution and no significant inflammation, as confirmed by histological analysis.

Conclusions:

• Chitosan-coated nanoparticle-embedded microspheres (CNP-MS) are suitable for local lung delivery.
• This system effectively enhances the cytotoxicity of 2-methoxyestradiol (2-ME) for lung cancer treatment.
• 2-ME CNP-MS demonstrate potential as a safe and effective inhalation agent for targeted lung cancer therapy.