A Novel Solubility-Enhanced Rubusoside-Based Micelles for Increased Cancer Therapy

Abstract

Many anti-cancer drugs have a common problem of poor solubility. Increasing the solubility of the drugs is very important for its clinical applications. In the present study, we revealed that the solubility of insoluble drugs was significantly enhanced by adding rubusoside (RUB). Further, it was demonstrated that RUB could form micelles, which was well characterized by Langmuir monolayer investigation, transmission electron microscopy, atomic-force microscopy, and cryogenic transmission electron microscopy. The RUB micelles were ellipsoid with the horizontal distance of ~25 nm and vertical distance of ~1.2 nm. Insoluble synergistic anti-cancer drugs including curcumin and resveratrol were loaded in RUB to form anti-cancer micelles RUB/CUR + RES. MTT assay showed that RUB/CUR + RES micelles had more significant toxicity on MCF-7 cells compared to RUB/CUR micelles + RUB/RES micelles. More importantly, it was confirmed that RUB could load other two insoluble drugs together for remarkably enhanced anti-cancer effect compared to that of RUB/one drug + RUB/another drug. Overall, we concluded that RUB-based micelles could efficiently load insoluble drugs for enhanced anti-cancer effect.Electronic supplementary materialThe online version of this article (doi:10.1186/s11671-017-2054-4) contains supplementary material, which is available to authorized users.

Anti-cariogenic Characteristics of Rubusoside

“…It is a well-known natural nontoxic sweetening agent. It has been used in various food and beverage products [8]. In addition, Ru has been used to increase the solubility of several pharmaceutically and medically important compounds with poor solubility in water [9].…”

“…Ru is well-known as a solubilizer for insoluble compounds [9,21]. Curcumin is a compound that has low solubility in water (Zhang et al 2017). The MIC value of curcumin has been reported against S. mutans [22,23].…”

Novel self-nanomicellizing solid dispersion based on rebaudioside A: a potential nanoplatform for oral delivery of curcumin

“…These novel ultrasmall micelles showed an appreciable ability to encapsulate hydrophobic molecules such as Coumarin 6 (a fluorescent marker widely used as a substitute for hydrophobic drugs in in vitro and/or in vivo experiments owing to its high fluorescence activity and biocompatibility). 3 All our previous findings indicated that RA micelle formulations have great potential to serve as novel nano-drug delivery systems that can improve the bioavailability of hydrophobic drugs. 4 However, the potential of RA as a nanocarrier of an active pharmaceutical ingredient still requires evaluation.…”

Temperature-Dependent Dynamical Evolution in Coum/SBE-β-CD Inclusion Complexes Revealed by Two-Dimensional FTIR Correlation Spectroscopy (2D-COS)

“…Over the last years, many efforts have been devoted to the design of high-performance drug delivery systems capable to transport suitable dosage of the drug with high spatial and temporal accuracy. As is well-known, drugs administered through conventional routes may lead to a series of unwanted effects mainly induced by their poor water solubility in lipophilic solvents and insufficient bioavailability [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ], strongly limiting their pharmacological efficacy. In this context, supramolecular compounds based on natural and modified cyclodextrins (CDs and MCDs, respectively) represent an attractive strategy for the engineering of bio-friendly host-guest inclusion complexes capable to improve the chemical/physical properties of pharmaceutical agents both in solution or in solid state [ 8 , 9 , 10 , 11 , 12 ].…”