Drug Delivery System For Cancer Chemotherapy Research Articles

PH-Responsive Vesicle Formation by PEGylated Cholesterol Derivatives: Physicochemical Characterization, Stability, Encapsulation, and Release Study.

PEGylated vesicles are known to serve as blood-persistent drug-delivery systems (DDSs) with potential applications in intravenous drug administration. pH-responsive PEGylated vesicles are also among the most promising stimuli-responsive carriers for drug delivery and controlled release for cancer chemotherapy. Herein, we report design and synthesis of two novel pH-responsive amphiphiles by coupling a cholesterol (Chol) and poly(ethylene glycol) chain with l-cysteine amino acid through hydrolysable linkages. The objective of this work is to physicochemically characterize the nanoaggregates of the amphiphiles under different experimental conditions. We have demonstrated spontaneous vesicle formation by the amphiphiles in water using various spectroscopic, calorimetric, and microscopic techniques. The size of vesicles was observed to increase on reduction of solution pH and increase in amphiphile concentration. The vesicles were found to be sufficiently stable under physiological conditions and were shown to be able to encapsulate not only hydrophilic dyes in their aqueous core but also hydrophobic guest molecules in the bilayer membrane constituted by the Chol units. These nanosized vesicles exhibit pH-triggered release of encapsulated dye molecules in acidic pH. Thus, these spontaneously formed stable vesicles might hold potential as biocompatible DDSs in cancer chemotherapy.

Soluplus/TPGS mixed micelles for dioscin delivery in cancer therapy

Background: Dioscin has shown cytotoxicity against cancer cells, but its poor solubility and stability have limited its clinical application. In this study, we designed mixed micelles composed of TPGS and Soluplus® copolymers entrapping the poorly soluble anticancer drug dioscin.Method: In order to improve the aqueous solubility and bioactivity of dioscin, TPGS/Soluplus® mixed micelles with an optimal ratio were prepared using a thin-film hydration method, and their physicochemical properties were characterized. Cellular cytotoxicity and uptake of the dioscin-loaded TPGS/Soluplus® mixed micelles were studied in MCF-7 breast cancer cells and A2780s ovarian cancer cells. The pharmacokinetics of free dioscin and dioscin-loaded TPGS/Soluplus® mixed micelles was studied in vivo in male Sprague-Dawley rats via a single intravenous injection in the tail vein.Results: The average size of the optimized mixed micelle was 67.15 nm, with 92.59% drug encapsulation efficiency and 4.63% drug loading efficiency. The in vitro release profile showed that the mixed micelles presented sustained release behavior compared to the anhydrous ethanol solution of dioscin. In vitro cytotoxicity assays were conducted on human cancer cell lines including A2780s ovarian cancer cells and MCF-7 breast cancer cells. The mixed micelles exhibited better antitumor activity compared to free dioscin against all cell lines, which may benefit from the significant increase in the cellular uptake of dioscin from mixed micelles compared to free dioscin. The pharmacokinetic study showed that the mixed micelle formulation achieved a 1.3 times longer mean residual time (MRT) in circulation and a 2.16 times larger area under the plasma concentration–time curve (AUC) than the free dioscin solution.Conclusion: Our results suggest that the dioscin-loaded mixed micelles developed in this study might be a potential nano drug-delivery system for cancer chemotherapy.

Study on antitumor activity of paclitaxel-loaded polymeric micelles

Objective To develop paclitaxel-loaded polymeric micelles from poly (e-caprolactone)-poly (ethylene glycol)-poly(e-caprolactone) (PCL-PEG-PCL),and to evaluate in vitro cytotoxicity as well as in vivo antitumor activity against EMT-6 tumor breast cell.Methods Paclitaxel-loaded polymeric micelles were prepared by thin-film hydration and ultrasonic method.The physical status of paclitaxel inside the polymeric micelles was investigated by differential scanning calorimetry (DSC).In vitro cytotoxicity of paclitaxel-loaded polymeric micelles against EMT-6 cell line was assessed by MTT assay.In vivo anticancer activity was evaluated against EMT-6 tumorbearing mice,with commercially available Taxol injection as control.Results Paclitaxel-loaded polymeric micelles exhibited homogeneous spherical shapes with apparent core-shell morphology.The average diameter of paclitaxelloaded polymeric micelles was 93 nm.DSC study indicated that paclitaxel was in solid amorphous state after being encapsulated in the polymeric micelles.In vitro cytotoxicity demonstrated that the cytotoxic effect of paclitaxelloaded polymeric micelles was lower than that of Taxol injection at the same paclitaxel content.Paclitaxel-loaded polymeric micelles showed greater tumor growth-inhibition effect in vivo on EMT-6 breast tumor in comparison with that of Taxol injection,with tumor growth inhibition of 85.79％ and 63.37％,respectively (P＜0.05).Conculsions The prepared paclitaxel-loaded polymeric micelles showed high anti-tumoral efficacy and low toxicity,and might have the potential to be developed as an effective anticancer drug-delivery system for cancer chemotherapy. Key words: Polymeric micelles; PCL-PEG-PCL; Paclitaxel; Anti-tumoral effect