Cyclodextrin-in-Liposome for therapy: Advances and challenges

The concept of drug-in-cyclodextrin-in-liposomes (DCLs) was introduced to the scientific community thirty years ago by McCormack and Gregoriadis (1994). Since then, there have been ongoing advances in cyclodextrin (CD) and liposome technology. Various CD derivatives and subtypes of liposomes have emerged. CDs are known nowadays as sequestering agents of cholesterol from tissues and as solubilizers of many hydrophobic active compounds. However, CDs have poor bioavailability, which limits their oral administration. Moreover, CD/drug inclusion complexes are limited as controlled delivery systems due to their rapid dissociation in blood. On the other hand, hydrophobic drugs embedded in the lipid bilayer of liposomes may affect the lipid membrane stability and exhibit a low loading rate. This review focuses on the advantages that CD-in-liposomes (CLs) offer to the medical field as carriers that can transport CDs in either their free forms or as CD/drug inclusion complexes. Liposomes can also embed specific molecules on their surfaces, enabling targeting, which remains to date a challenge for modified CDs. This review summarizes the literature on the use of CL- or DCL-based formulations aimed at treating certain diseases and the mechanisms underlying their distribution and function.