POxylated Dendrimer-Based Nano-in-Micro Dry Powder Formulations for Inhalation Chemotherapy.

Area of Science:

• Nanotechnology and Drug Delivery
• Biomedical Engineering
• Pharmacology

Background:

• Lung cancer remains a significant health challenge, necessitating advanced drug delivery systems.
• Current chemotherapy delivery methods often face limitations in targeting and efficacy.
• Nanoparticle-based systems offer potential for improved therapeutic outcomes in lung adenocarcinoma.

Purpose of the Study:

• To develop respirable, biocompatible, and biodegradable dry powder formulations (DPFs) for deep lung delivery of chemotherapeutics.
• To encapsulate paclitaxel (PTX) and doxorubicin (DOX) within polyurea dendrimer nanoparticles (PURE_G4OOx₄₈) and micronize them with chitosan (CHT).
• To evaluate the in vitro cytotoxicity and chemotherapeutic effect of these nanoparticle formulations in lung adenocarcinoma cells.

Main Methods:

• Supercritical CO₂-assisted spray drying (SASD) was employed to create dry powder formulations.
• POxylated polyurea dendrimer (PURE_G4OOx₄₈) nanoparticles were loaded with paclitaxel (PTX) and doxorubicin (DOX).
• Micronization of nanoparticles with chitosan (CHT) was performed.
• In vitro cytotoxicity assays were conducted using a lung adenocarcinoma cell line.

Main Results:

• DOX-loaded PURE_G4OOx₄₈ nanoparticles exhibited significantly higher cytotoxicity compared to free doxorubicin.
• The dry powder formulations (DPFs) did not display increased cytotoxicity compared to their respective nanoparticles.
• DOX-DPFs demonstrated a superior chemotherapeutic effect over PTX formulations in adenocarcinoma cells.

Conclusions:

• Supercritical CO₂-assisted spray drying is an effective method for producing respirable, nanoparticle-based dry powder formulations for lung delivery.
• The developed DOX-loaded nanoparticles show enhanced efficacy for treating lung adenocarcinoma.
• These findings suggest a promising strategy for targeted chemotherapy delivery to the deep lung.