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A promising co-delivery system was proposed for effectively reversing multidrug resistance of cancer cells and simultaneously improving the anticancer effect of the drug.

In this paper, we successfully synthesized folate-modified pH-sensitive copolymer methoxy-poly(ethylene glycol)2K-poly(ε-caprolactone)4K-poly(glutamic acid)1K (mPEG2K-PCL4K-PGA1K-FA), which could form the polymeric assembly in an aqueous solution, for co-delivering hydrophilic drugs doxorubicin hydrochloride (DOX) and verapamil hydrochloride (VER) (FA-poly(DOX+VER)). Since VER was an effective P-glycoprotein inhibitor, the combination of DOX and VER could reverse the multidrug resistance efficiently and enhance the therapeutic effect. Therefore, the inhibition ratios of MCF-7/ADR resistant cancer cell treated by FA-poly (DOX+VER) were almost more than 30% higher than those of FA-polyDOX after 48h and 72h. Furthermore, the conjugation of FA could lead the co-delivery systems actively targeting into the FA receptor over-expressing cancer cells in addition to the passive accumulation of the assembly in tumor tissues. Importantly, the prepared mPEG2K-PCL4K-PGA1K-FA assembly showed high pH-sensitive property, which made the drugs mostly released in tumor tissue (acid environment) than in physiological environment (neutral environment). In summary, the as-prepared co-delivery system FA-poly(DOX+VER) demonstrated a high efficiency in reversing the multidrug resistance and targeting FA receptor to improve the anticancer effect of DOX in MCF-7/ADR resistant cells.

In this work we designed a controlled-release drug delivery system formed by a cationic drug (diphenhydramine hydrochloride, DH) and an anionic surfactant (sodium 2-ethylhexyl sulfosuccinate, AOT) and investigated the corresponding physicochemical properties, aggregation behavior and potential application in drug delivery systems. The DH-AOT mixed solutions with different molar ratios of DH and AOT at the same total concentration were prepared and characterized. The aggregation behaviors of the drug/surfactant solutions were studied by transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential techniques. Furthermore, hemolysis testing, and in vitro and in vivo drug release were studied to evaluate the potential use of the as-prepared catanionic aggregates in drug delivery systems. The results indicate that the physicochemical properties, the hemolytic toxicity and the drug release behavior are dependent on the composition of the samples, X 1 (X 1 ¼ n DH /n (DH+AOT) ). The results demonstrated that these drug-participating catanionic aggregates show potential as an efficient and safe sustained drug delivery system.