A Systematic Approach for Liposome and Lipodisk Preclinical Formulation Development by Microfluidic Technology

Area of Science:

• Drug Delivery and Nanotechnology
• Pharmaceutical Sciences
• Biophysical Chemistry

Background:

• Lipid nanoparticles (LNPs) are crucial for enhancing therapeutic drug performance, but their development, particularly for complex systems like liposomes, is material and time-intensive.
• Optimizing encapsulation efficiency (EE) is vital for the commercial viability of LNP-based therapeutics.
• Existing methods for LNP formulation can be resource-intensive, necessitating more efficient development strategies.

Purpose of the Study:

• To develop a decision tree to guide the optimization of encapsulation efficiency (EE) for liposome and lipodisk formulations.
• To investigate the relationship between compound physicochemical properties (e.g., Log P) and their encapsulation efficiency in different lipid-based drug delivery systems.
• To establish a systematic approach for resourceful formulation development of lipid-based drug delivery systems.

Main Methods:

• Utilized microfluidic techniques for reproducible fabrication of liposome and lipodisk formulations.
• Employed a range of model compounds with diverse physicochemical properties, including varying Log P values.
• Systematically altered drug/lipid (D/L) ratios and polyethylene glycol (PEG) lipid concentrations to assess their impact on EE.

Main Results:

• Higher Log P compounds (e.g., curcumin) showed high EE in liposomes, influenced by D/L ratio.
• Moderate Log P compounds (e.g., cyclosporine A, dexamethasone) exhibited higher EE in lipodisks due to increased PEG lipid content.
• Low Log P compounds (e.g., acyclovir) consistently displayed low EE across tested conditions.
• Curcumin-loaded liposomes and lipodisks demonstrated improved in vivo pharmacokinetic performance in rats compared to conventional formulations.

Conclusions:

• The developed decision tree provides systematic guidance for optimizing EE in lipid-based drug delivery systems.
• Understanding compound physicochemical properties is key to selecting the appropriate LNP formulation (liposome vs. lipodisk) for efficient drug loading.
• This approach facilitates resourceful development, minimizes drug waste, and accelerates preclinical development for industrial compounds.