Microencapsulated Chitosan-Based Nanocapsules: A New Platform for Pulmonary Gene Delivery

Area of Science:

• Biomaterials Science
• Nanotechnology
• Pulmonary Drug Delivery

Background:

• Pulmonary gene delivery faces challenges in efficient and homogeneous transfection of lung epithelial cells.
• Chitosan (CS)-based nanocarriers offer potential for gene delivery due to their biocompatibility and mucoadhesive properties.
• Hyaluronic acid (HA) incorporation may enhance cellular uptake and targeting in the lung.

Purpose of the Study:

• To develop and evaluate chitosan-based nanocapsules (NCs) for pulmonary gene delivery.
• To investigate the role of hyaluronic acid (HA) in enhancing gene transfection efficiency in the lung.
• To create a micro-nanostructured platform for efficient delivery of genetic material to deep lung tissues.

Main Methods:

• Chitosan (CS)-based nanocapsules (NCs) were formulated and loaded with a model plasmid (pCMV-βGal).
• Plasmid encapsulation efficiency was determined.
• NCs were microencapsulated into mannitol (Ma) microspheres (MS) via spray-drying for pulmonary administration.
• In vivo transfection efficiency and distribution were assessed in the lung.

Main Results:

• Plasmid encapsulation efficiency in CS-based NCs reached approximately 90%.
• The micro-nanostructured platform successfully delivered NCs to the deep lung.
• Hyaluronic acid-containing HA/CS NCs demonstrated superior, more homogeneous transfection efficiency in alveolar cells compared to controls.
• The formulation achieved transfection in a more extended lung area.

Conclusions:

• Chitosan-based nanocapsules, particularly those incorporating hyaluronic acid, represent an effective strategy for pulmonary gene delivery.
• The developed micro-nanostructured platform enhances the homogeneous transfection of lung alveolar cells.
• This approach holds significant promise for the therapeutic treatment of genetic lung diseases.