Lipidic Cubic‐Phase Nanoparticles—Cubosomes for Efficient Drug Delivery to Cancer Cells

Abstract

Self‐assembled lipid liquid‐crystalline nanoparticles, known as cubosomes, were used for the delivery of the anticancer drug doxorubicin (DOX). Several properties make cubosomes a promising alternative in the development of controlled‐release systems for drug delivery. They have a larger internal surface area than other carriers, hence deliver more drug molecules to the affected cells and maintain the cubic symmetry of the parent lipidic cubic phase, but at the same time they have a lower viscosity thereby facilitating transport of the drug. The pH‐dependent drug release profiles, evaluated by voltammetry, demonstrated triggered drug release from the cubosome carrier to the environment of the cancer cells, where pH is lower. The anticancer effect of a DOX‐loaded cubosome on the glioblastoma T98G cell line was found to be highly efficient and required lower concentrations of DOX to inhibit the proliferation of cancer cells than the effective concentrations of free DOX.

Theranostic combinatorial drug-loaded coated cubosomes for enhanced targeting and efficacy against cancer cells

“…This study underlines the importance of cubosomes as an efficient nano drug carrier, especially for the hydrophobic drugs. This is in line with the various other studies where cubosomes acted as nanovehicles for anticancer drugs 25,27,46 . This study may also act as guide to design combinatorial drug-loaded coated cubosomes for therapeutic approaches toward cancer.…”

“…The cytotoxicity results suggest coated cubosomes have lower toxicity compared with uncoated ones, but it is also evident that there is a significant difference between the cytotoxicity of coated and uncoated cubosomes. This is an interesting find since there are reports that cubosomes have higher toxicity than monooleins combined with drug 46,47 . Therefore, it was highlighted by our study that coating may reduce the cytotoxicity of the cubosomes too.…”

Cubosomes: The Next Generation of Smart Lipid Nanoparticles?

“…[69,70] To date the majority of reports of loaded cubosomes are of proteins or small molecules incorporated within the lipid membrane and predominantly use single or binary lipid compositions based on monoolein or phytantriol. There have been numerous reports of cubosome systems loaded with small molecules, including cancer drugs, [32,49,105] aspirin, [106] antimicrobial peptides, [107,108] and of acting as potentiators for the delivery of immunostimulants. [109] The reported encapsulation efficiencies are in the range 71-103% for the anti-cancer drugs, [32,49,103,105] and aspirin was reported to have an encapsulation efficiency of 61.9-71.6%.…”

“…There have been numerous reports of cubosome systems loaded with small molecules, including cancer drugs, [32,49,105] aspirin, [106] antimicrobial peptides, [107,108] and of acting as potentiators for the delivery of immunostimulants. [109] The reported encapsulation efficiencies are in the range 71-103% for the anti-cancer drugs, [32,49,103,105] and aspirin was reported to have an encapsulation efficiency of 61.9-71.6%. [106] Interestingly, for water soluble antimicrobial peptides that associate with the cubosome membrane surface, the association efficiency was highly dependent on the peptide ranging from 7 to more than 60%.…”

“…Cancer therapeutics are the most widely reported application of cubosome systems. In vitro cubosomes have been loaded with cancer drugs including Doxorubicin, [105] Sorafenib, [133] 5-Fluorouracil, [134,135] and Quercetin [49] and delivered to cell lines including human hepatocellular carcinoma (HepG2) cells, glioblastoma T98G cells and mouse 3T3 fibroblasts. [49] Tumor cells have more acidic environments making pH stimuli useful for the payload delivery of chemotherapeutics.…”