By Zelihagül Değim
Cancer is a major cause of mortality, and more than 10 million people are diagnosed with it annually. Breast cancer currently shows the highest incidence of death in women, after lung cancer. Over a third of women with breast cancer are considered to develop a metastatic disease, and the average survival time from diagnosis to recurrence for cancer patients is reported to be between 18 and 30 months. There is a general need to use known chemicals to develop an effective drug with effective delivery for better therapy. In this particular concern, lipophyllic delivery systems may be more effective than hydrophyllic ones, and we think that liposomes or cochleates may be good candidates.
Liposomes are known as spherical vesicular lipid-based carrier systems, and they have been used to increase permeability and bioavailability because of structural similarities with biological cell membranes. Cochleates are a relatively new type of crystalline particles having large and continuous lipid bilayer sheets rolled up in a spiral structure with no large internal aqueous phases. Both have nonaqueous structures, and cochleates are more stable because of the less oxidation potential of lipids. Cochleates exhibit efficient incorporations of hydrophobic drug molecules into the lipid layers in the structure, and they have another potential for slow release. Lipid layers of cochleates are accepted to be nontoxic.
Cochleates have some extraordinary effects in living cells: They have a spiral tubular shape and may act as microneedles because at the front edge of the cochleates, all electrochemical and thermodynamic forces come through the longitudinal part and those forces make the tip of the cochleates very strong and active. When cochleates approach the cell membrane, this force makes the cell membrane very flexible and unstable; therefore, the surface tension of the cell membrane reduces and the membrane bends spontaneously through the internal side. A kind of insertation/perturbation of cochletaes occurs. Conditions in the interior of the membrane may be more preferable for the active molecules, and cochleates may then release/inject the contents to the interior side. Therefore, the permeability of the active substance can be found high.
In our recent study published in AAPS PharmSciTech, liposome and cochleate formulations containing raloxifene, a breast cancer therapy, have been developed. The highest antitumor activity was found with raloxifene-loaded cochleates containing dimethyl-β-cyclodextrin. We also believe that this report can provide new information about the effectiveness of liposomes and cochleates for drug delivery and possible mechanisms. Potential mechanisms and related interpretations can be found in the manuscript.