Spin label partitioning in lipid vesicles. A model study for drug encapsulation

Area of Science:

• Biochemistry
• Materials Science
• Physical Chemistry

Background:

• Lipid vesicles are crucial for drug delivery and biomimetic systems.
• Controlling molecule encapsulation and release is essential for vesicle functionality.
• Understanding factors influencing encapsulation efficiency is an ongoing research area.

Purpose of the Study:

• To identify key features governing small molecule encapsulation into lipid vesicles.
• To investigate the impact of molecule hydrophobicity and bilayer properties on encapsulation and release.
• To compare encapsulation in multilamellar and unilamellar vesicles.

Main Methods:

• Synthesis of spin labels from five carboxylic acids of varying lengths.
• Incorporation of spin labels into multilamellar and unilamellar vesicles composed of four phosphatidylcholines.
• Systematic study of bilayer rigidity and entrapped molecule hydrophobicity on release.
• Estimation of hydrophobicity using partition coefficients (P) between octanol and buffer.

Main Results:

• Molecule hydrophobicity is critical; extreme partition coefficient values (log P < -0.3 or > 5) favor efficient entrapment in multilamellar vesicles.
• Leakage rates exhibit a bell-shaped correlation with the partition coefficient.
• Gel state bilayers and long lipid acyl chains promote better entrapment.
• Unilamellar vesicle formation is possible with high spin label concentrations but reduces internal volume and entrapped water-soluble molecules.

Conclusions:

• Hydrophobicity and lipid chain length significantly influence small molecule encapsulation and release kinetics in lipid vesicles.
• The type of vesicle (multilamellar vs. unilamellar) impacts encapsulation efficiency and internal volume.
• Optimizing vesicle composition and molecule properties is vital for controlled encapsulation and delivery applications.