Double loading of cyclosporine A in liposomes using cyclodextrin complexes

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Liposome Technology

Background:

• Efficient encapsulation of therapeutic agents in liposomes is crucial for drug delivery.
• Cyclosporine A (CyA) benefits from liposomal encapsulation due to reduced side effects.
• Increasing lipophilic drug aqueous solubility can enhance liposomal encapsulation.

Purpose of the Study:

• To investigate the use of cyclodextrins (CDs) for complexing CyA to increase its aqueous solubility.
• To enhance liposomal loading of CyA by utilizing CyA-CD complexes.
• To evaluate the effects of CyA loading on liposome characteristics, stability, and drug release.

Main Methods:

• Preparation of liposomes encapsulating CyA, CyA-CD complexes, and double-loaded liposomes.
• Evaluation of liposomal characteristics, including drug entrapment efficiency and bilayer integrity via carboxyfluorescein (CF) leakage.
• Analysis of drug release profiles for all liposomal formulations.

Main Results:

• Liposomes formulated with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC):cholesterol (CHOL) (1:1) and hydrogenated soybean phosphatidylcholine (HSPC):CHOL (1:1) showed maximum CyA entrapments of 65.94% and 75.03%, respectively.
• Encapsulation efficiency for CyA-CD complexes was not significantly different across formulations; however, double-loaded liposomes showed approximately a 2-fold increase in drug entrapment.
• Drug release was biphasic for all formulations. CyA-CD complexes exhibited faster initial release, and CD inclusion affected liposome permeability, with double-loaded liposomes showing maximum CF leakage.

Conclusions:

• Complexing CyA with CDs increases its aqueous solubility, enabling co-encapsulation in both aqueous and lipid bilayers of liposomes.
• Higher drug entrapment was achieved using CyA-CD complexes, particularly in double-loaded liposomes.
• The enhanced drug loading compromised liposome stability, necessitating careful consideration in formulation development.