Modified liposomes for improved drug loading and sustained drug release

Background

Liposomes are a promising method of drug delivery, offering better properties than traditional drug delivery systems. However, despite having better site-targeting, protection from drug degradation, improved sustained or controlled release, and lower toxicity, some challenges remain. For example, insufficient drug loading and leakage of payload remain major challenges in the design of liposome-based drug delivery systems. These phenomena can limit the duration of the effect of the drug and cause toxicity in patients. Some efforts have been made to improve drug release kinetics from liposomes and to improve their sustained release capabilities, however these methods have major limitations that make large scale production difficult and raise concerns for quality assurance and cost. A simple and effective approach to improve the drug loading and controlled drug release ability of liposomes would therefore be a substantial improvement over current methods.

Technology Overview

Targeting the rate-limiting step in drug release from liposomes, Boston Children’s Hospital researchers invented intra-bilayer modified liposomes for improved drug loading and sustained drug release. A strategy for synthesizing acyl chain-modified phospholipids with terminal functional groups was used.

Formulation of acyl chain-modified phospholipids and natural phospholipids allowed the formation of aromatized bilayer vesicles with similar morphology, size, and surface charge to conventional liposomes but significantly decreased membrane permeability and leakage of encapsulated payload. Proof-of-concept studies also showed that these formulations enabled increased drug loading, prolonged therapeutic duration, expanded the therapeutic window, and mitigated systemic toxicity.

Applications

This invention can be used for the delivery of a variety of therapeutics including:

• Local anesthetics
• Chemotherapeutics
• Macromolecular drugs
• Protein drugs

Advantages

• Increased drug loading efficiency and reduced leakage
• Controlled drug release with reduced systemic toxicity
• Prolonged therapeutic duration and expanded therapeutic window
• Potential for delivering a broad range of therapeutic agents including local anesthesia

Publications

Li, Y., Ji, T., Torre, M., Shao, R., Zheng, Y., Wang, D., Li, X., Liu, A., Zhang, W., Deng, X., Yan, R., & Kohane, D. S. (2023). Aromatized liposomes for sustained drug delivery. Nature communications, 14(1), 6659. https://doi.org/10.1038/s41467-023-41946-8