Formulation and manufacturing of lymphatic targeting liposomes using microfluidics

Area of Science:

• Nanotechnology
• Biomedical Engineering
• Pharmacology

Background:

• Lymphatic targeting is crucial for therapies like cancer treatment and vaccination.
• Vesicle size and charge influence lymphatic uptake and distribution.
• Developing effective liposomal systems for lymphatic delivery remains a challenge.

Purpose of the Study:

• To develop and optimize liposomal formulations for enhanced lymphatic targeting and retention.
• To investigate the impact of liposome charge and size on lymphatic biodistribution.
• To incorporate an avidin/biotin system for improved liposome retention and to utilize microfluidics for protein loading.

Main Methods:

• Screening of neutral, cationic, and anionic liposomes for lymphatic targeting.
• Biodistribution studies following intramuscular injection.
• Utilizing microfluidics for the production of small, biotinylated liposomes loaded with protein.
• Employing an avidin/biotin complex to enhance liposome retention in lymphatics.

Main Results:

• Anionic liposomes demonstrated the most rapid clearance to draining lymphatics.
• Smaller unilamellar vesicles achieved high lymphatic targeting, increasing concentration by 10-fold.
• The avidin/biotin system successfully enhanced retention of liposomes and entrapped protein in lymph nodes.
• Microfluidics enabled efficient protein incorporation into ~90nm biotinylated liposomes.

Conclusions:

• Liposome charge and size are critical factors for effective lymphatic targeting.
• An avidin/biotin complex significantly improves liposome retention within the lymphatic system.
• Microfluidics is a viable method for producing protein-loaded liposomes with enhanced lymphatic delivery and retention properties.