Multifunctional redox-responsive and CD44 receptor targeting polymer-drug nanomedicine based curcumin and alendronate: synthesis, characterization and in vitro evaluation.

The traditional therapy of cancer has systemic side effects, and many cancers, such as human breast cancer and lung cancer easily metastasize to bones, leading to the formation of secondary tumours. This study was aimed at enhancing the anti-tumour effect of curcumin (CUR) and preventing tumour spread to the bone. A novel multifunctional redox-responsive and CD44 receptor targeting polymer-drug, poly alendronate-hyaluronan-S-S-curcumin copolymer (ALN-oHA-S-S-CUR) based CUR and alendronate (ALN) were synthesized successfully with the disulphide bond linker. The structure of ALN-oHA-S-S-CUR was characterized by 1H-NMR. The nanomedicine had natural anti-tumour drugs (CUR) as the hydrophobic kernel, and targeting CD44 receptor oligosaccharides of hyaluronan (oHA) and other anti-tumour drugs (ALN) as hydrophilic shell, named ALN-oHA-S-S-CUR conjugates, which could self-assemble into micelle-like nano-spheres in water via a dialysis method with hydrodynamic diameters of 179 ± 23 nm. Interestingly, the cur-loaded ALN-oHA-S-S-CUR micelles were stable in PBS but were capable of releasing the drug under the reducing environment. The rate of drug release was proportional to the GSH concentration. The uptake and cytotoxicity of micelles were higher in MDA-MB-231 cells than in MCF-7 cells because of a higher expression of the CD44 receptor in the former cell line. And compared to the cur-loaded oHA-CUR micelles, the cur-loaded ALN-oHA-S-S-CUR micelles had a good cellular uptake in 2D cancer cell and penetrability in 3D cancer cell spheroids. These results indicated the active targeting redox-sensitive micelles were promising as intracellular drug delivery systems for cancer treatment.

Synthesis, Characterization and In Vitro Evaluation of Dual pH/Redox Sensitive Marine Laminarin-Based Nanomedicine Carrier Biomaterial for Cancer Therapy.

In order to improve the anti-cancer therapy efficiency of hydrophobic drugs such as curcumin (Cur), a novel dual pH/redox sensitive marine laminarin-based nanomedicine carrier biomaterial with photo-dynamic therapy (PDT) was synthesized in this study. The new synthetic chemical structure, named as Hematin-Laminarin-Dithiodipropionic Acid-MGK (HLDM), was characterized by 1H-NMR and IR. The Cur-loaded micelles were then prepared via dialysis method. The HLDM could self-assemble into micelles in water with hydrodynamic diameter of 135±15 nm. The particle size, zeta potential and morphology of micelles were detected by transmission electron microscope (TEM). Interestingly, the in vitro release experiment showed that the release amount of Cur-loaded HLDM micelles could reach 80% in the pH and redox sensitive environment. Furthermore, cell study showed that the Cur-loaded HLDM micelles had stronger cellular uptake and cytotoxicity to MCF-7 cells than that of HLDM. The multifunctional marine laminarin based nanomedicine carrier biomaterial can be used for new drug delivery systems with dual pH/redox sensitivity for cancer therapy.

Formulation and in vitro evaluation of quercetin loaded polymeric micelles composed of pluronic P123 and D-a-tocopheryl polyethylene glycol succinate.

The objective of this study was to develop a polymeric delivery system to improve the solubility and biological activity of Quercetin (QT). QT loaded mixed micelles, composed of Pluronic P123 (P123) and D-a-tocopheryl polyethylene glycol succinate (TPGS) with proportion of 7:3 (QT-P/T), were prepared by thin-film hydration method. The average size of the mixed micelles was 18.43 nm, and the encapsulating efficiency for QT was 88.94 +/- 3.71%, drug-loading was 10.59 +/- 0.38%. The solubility of QT in QT-P/T was 5.56 mg/mL, which was about 2738-fold that of crude QT in water. Compared with the QT propylene glycol solution, the in vitro release of QT from QT-P/T presented the sustained-release property. The in vitro cytotoxicity assay showed that the IC50 values on MCF-7 cells for QT-P/T and QT loaded P123 micelles (QT-P123) were 7.13 microg/mL and 10.73 microg/mL, respectively, while 7.23 microg/mL and 14.47 microg/mL on MCF-7/ADR cells. From the results, it can be concluded that, P123/TPGS mixed micelles may serve as a pharmaceutical nano carrier with improved solubility and biological activity for QT.