| Among various drug delivery formulations, redox-sensitive drug-loaded nanoparticles (NPs) have drawn rapidly interesting attention. They can release the drug efficiently triggered by the high redox potential difference between the reducing intracellular space and oxidizing extracellular space,and lead to optimal therapeutic efficacy with reduced side effects. Therefore, the synthesis of redox-sensitive and biocompatible polymers, as well as their nanostructure preparation for anticancer drug delivery gain popularity.In this study, a new disulfide-linked diblock polymer of MPEG and PLA (MPEG-SS-PLA) was successfully synthesized. The synthesized redox-responsive polymer MPEG-SS-PLA possesses reducibility to a reducing agent. Using the oil-in-water (O/W) emulsion/solvent evaporation method and the synthesized polymer MPEG-SS-PLA, series of Paclitaxel (PTX)-loaded MPEG-SS-PLA nanoparticles (MPEG-SS-PLA NPs) were prepared in the presence of varying weight percentages of PTX (PTX/polymer, 1%, 3%, 5% and 10%). Their size and morphology were characterized using a scanning electron microscope, indicating that the prepared PTX-loaded NPs were dispersed as individual particles and with a rice-like shape. The increased feed ratio (PTX/polymer) resulted in larger particles. Especially, NPs pepared with the feed ratio of 5% and 10% were notably larger. The mean partcle major axis lengths were 1169.1±9.9 nm, 2217.4±43.9 nm and minor axis lengths were 145.4±3.7 nm, 159.6±2.0 nm, respectively. PTX loading efficiency (LE), encapsulation efficiency (EE), stability of PTX-loaded NPs as well as in vitro PTX release were analyzed using high-performance liquid chromatography. The prepared PTX-loaded polymeric NPs possess high PTX EE ranging from 80% to 90%. PTX-loaded MPEG-SS-PLA NPs have long-term stability (at least 3 months at -20°C), which also facilitate their next investigation. In vitro PTX release study exhibited that the PTX-loaded MPEG-SS-PLA NPs reached almost 90% PTX release within 96 h when GSH presented at an intracellular concentration, whereas only a very minor amount of PTX (35%) was released at plasma GSH levels. In vitro cytotoxicity of PTX-loaded polymeric NPs was assessed using a standard Methyl Thiazolyl Tetrazoliun (MTT) assay against human lung adenocarcinoma epithelial cell line (A549 cells), hunman breast adenocarcinoma cell line (MCF-7 cells), and hunman cervical carcinoma cell line (Hela cells). The results demonstrated that the synthesized NPs material is lowly cytotoxic and has a highly cellular compatibility. There is no cytotoxic activity of 0.5 mg/mL-NPs when treating A549 cells and MCF-7 cells for 72 h. PTX-loaded MPEG-SS-PLA NPs could lead concentration- and time-dependent changes of cell viability. To investigate cellular uptake of PTX-loaded NPs, the fluorescent dye coumarin-6 was used as a model drug and the endocytosis assay was performed visually. The results showed a rapid penetration and intracellular accumulation of the redox-responsive NPs, as well as fast drug dispersing from NPs. All these results demonstrated that the synthesized redox-responsive polymer MPEG-SS-PLA, as well as its NPs could be utilized as a potential carrier for positioning delivery of antitumer drug. |
PDF Full Text Request