Posted by 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 with 103 references 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.
The current literature review has shown that drugs from different chemical classes and therapeutic targets can be encapsulated in CD-in-liposome and their performance has been evaluated in in vivo studies. However, searches in recognized clinical trial databases have revealed that CD-in-liposome, whether in its free form or as a drug-loaded formulation, has not yet entered clinical trials. It is currently documented that flexible DCL enhances skin permeation, positively charged DCL favors eye permeation, and PEG-ylated DCL is required for intravenous administration. For anticancer therapy, several studies proved the outperformance of DCL when compared to conventional liposome. These data highlight the need to translate preclinical findings into clinical studies involving approved drugs.
Petra Gerges, Raya Gerges, Paul Nguewa, Nabil ElKhoury, Sophie Fourmentin, Gustavo González-Gaitano, Helene Greige-Gerges (2029) Cyclodextrin-in-Liposome for therapy: Advances and challenges. Carbohydrate Polymers 372, 124573. https://doi.org/10.1016/j.carbpol.2025.124573