Surface-Modified Inhaled Microparticle-Encapsulated Celastrol for Enhanced Efficacy in Malignant Pleural Mesothelioma

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer.
• Celastrol (Cela) is a compound with demonstrated anti-cancer properties.
• Novel drug delivery systems are needed for effective MPM treatment.

Purpose of the Study:

• To develop inhaled Celastrol-loaded poly(lactic-co-glycolic) acid microparticles (Cela MPs) for MPM treatment.
• To characterize the physicochemical properties and pulmonary delivery suitability of Cela MPs.
• To evaluate the anti-mesothelioma efficacy and mechanism of action of Cela MPs.

Main Methods:

• Surface-modified Cela-loaded PLGA microparticles were prepared using a double emulsion solvent evaporation method.
• Physicochemical properties (entrapment efficiency, particle size, release profile) were analyzed.
• In vitro efficacy was assessed using mesothelioma cell lines, 3D spheroids, and mechanistic studies (antioxidant activity, apoptosis, autophagy).

Main Results:

• Optimized Cela MPs showed high entrapment efficiency and suitable aerodynamic diameter for pulmonary delivery.
• Cela MPs demonstrated significant anti-cancer activity against mesothelioma cell lines, reducing IC50 values.
• A single dose of Cela MP inhibited 3D spheroid growth, retained antioxidant activity, and induced apoptosis and autophagy.

Conclusions:

• Cela MPs are a promising inhalable formulation for MPM treatment.
• The developed microparticles exhibit potent anti-mesothelioma activity.
• Further investigation into Cela MPs as a therapeutic agent for MPM is warranted.