Peptide micelle-mediated curcumin delivery for protection of islet β-cells under hypoxia

Abstract

Islet transplantation is one of many therapeutic approaches for the treatment of diabetes. During transplant procedures, the isolated islets are subjected to hypoxic conditions, and undergo the apoptotic process. Curcumin has a cytoprotective effect, and may therefore be useful for the protection of islets under hypoxia. However, curcumin is hydrophobic, and an efficient curcumin carrier is required for effective treatment. In this study, R3V6 peptide micelles, composed of a 3-arginine stretch and 6-valine stretch, were evaluated as a curcumin carrier to INS-1 insulinoma cells. Curcumin was loaded into R3V6 micelles at a weight ratio of 10:3 (R3V6:curcumin). The size and surface charge of the curcumin-loaded R3V6 micelles (R3V6-curcumin) were approximately 250 nm and 17.49 mV, respectively. R3V6-curcumin delivered curcumin to the INS-1 cells more efficiently than either curcumin alone or a simple mixture of R3V6 and curcumin. MTT assay indicated that under hypoxia, R3V6-curcumin protected INS-1 cells more efficiently than curcumin alone. TUNEL and reactive oxygen species (ROS) assays suggested that R3V6-curcumin reduced INS-1 cell apoptosis under hypoxia. These results demonstrate that R3V6 peptide micelles are an effective carrier of curcumin, and that R3V6-curcumin may improve the viability of pancreatic β-cells in islet transplantation.

Cargo-Free Nanoparticles Containing Cationic Lipids Induce Reactive Oxygen Species and Cell Death in HepG2 Cells

“…7) However, it doesn't seem that any kind of micelles plays a role in stimulating ROS generation directly after uptake into cells, based on the suggestion that some specified micelles could be used to increase in cell viability under hypoxia. 36) Therefore, further analyses using various cationic lipids, including evaluation of NP-induced signaling in cells, should be performed to design effective NP formulations.…”

Antidiabetic Properties of Curcumin I: Evidence from In Vitro Studies

“…Treatment of INS-1 insulinoma cells with curcumin conjugated to R3V6 peptide micelles (10:3 weight ratio; 22 mg/L) for 24 h resulted in increased curcumin cellular uptake compared to curcumin treatment alone [114]. Hypoxic-induced cell viability was more significantly increased by both R3V6-curcumin than curcumin treatment alone.…”

“…Hypoxic-induced cell viability was more significantly increased by both R3V6-curcumin than curcumin treatment alone. In addition, R3V6-curcumin treatment reduced hypoxic-induced apoptosis and ROS production ( Table 4) [114].…”

Impact of Oxygen on Pancreatic Islet Survival

“…The organic compound, curcumin, was tested for its ability to protect β-cells from hypoxic injury. 84 As tested in INS-1 cells, curcumin administered through peptide micelles prevented β-cell apoptosis by suppressing ROS elevation. Metformin is known as a potent antihyperglycemic agent and improved insulin sensitivity in T1D patients.…”