Targeted Delivery of Doxorubicin-Loaded Poly (ε-caprolactone)-b-Poly (N-vinylpyrrolidone) Micelles Enhances Antitumor Effect in Lymphoma

Abstract

BackgroundThe present study was motivated by the need to design a safe nano-carrier for the delivery of doxorubicin which could be tolerant to normal cells. PCL63-b-PNVP90 was loaded with doxorubicin (6 mg/ml), and with 49.8% drug loading efficiency; it offers a unique platform providing selective immune responses against lymphoma.MethodsIn this study, we have used micelles of amphiphilic PCL63-b-PNVP90 block copolymer as nano-carrier for controlled release of doxorubicin (DOX). DOX is physically entrapped and stabilized in the hydrophobic cores of the micelles and biological roles of these micelles were evaluated in lymphoma.ResultsDOX loaded PCL63-b-PNVP90 block copolymer micelles (DOX-PCL63-b-PNVP90) shows enhanced growth inhibition and cytotoxicity against human (K-562, JE6.1 and Raji) and mice lymphoma cells (Dalton's lymphoma, DL). DOX-PCL63-b-PNVP90 demonstrates higher levels of tumoricidal effect against DOX-resistant tumor cells compared to free DOX. DOX-PCL63-b-PNVP90 demonstrated effective drug loading and a pH-responsive drug release character besides exhibiting sustained drug release performance in in-vitro and intracellular drug release experiments.ConclusionUnlike free DOX, DOX-PCL63-b-PNVP90 does not show cytotoxicity against normal cells. DOX-PCL63-b-PNVP90 prolonged the survival of tumor (DL) bearing mice by enhancing the apoptosis of the tumor cells in targeted organs like liver and spleen.

Downregulation of STAT3 phosphorylation enhances tumoricidal effect of IL-15-activated dendritic cell against doxorubicin-resistant lymphoma and leukemia via TNF-α

“…Doxorubicin-resistant (DOX-R) K-562 (K-562/DOX-R) and JE6.1 (JE6.1/DOX-R) were generated as described previously (Hira et al, 2014a). A detail methodology is described in supplementary materials and methods.…”

Self-assembling surfactant-like peptide A6K as potential delivery system for hydrophobic drugs

“…HepG2 cells were conventionally cultured to confluence, harvested, and adjusted to a density of 1×10 6 per mL. One milliliter of cells were transferred into a well of a 12-well plate, into which 20 μL of the suspension was added.…”

“…Despite the success of novel strategies such as soluble derivatives or prodrugs, [1][2][3] the strategy using a delivery system is still a predominant approach, particularly considering its potential to achieve targeted delivery or codelivery of different components. [4][5][6] In recent years, various types of materials have been investigated as delivery systems for hydrophobic drugs, including, but not limited to, liposomes, 7 polymeric nanoparticles, [8][9][10] hydrogels, 11,12 and carbon nanotubes. [13][14][15] Several wellstudied materials have been developed into clinically available formulations, such as Abraxane ® and Doxil ® .…”

Structural characterization and in vitro bioactivity assessment of SiO2–CaO–P2O5–K2O–Al2O3 glass as bioactive ceramic material

“…Tumor cells were plated (5 Â 10 3 cells/well) in a 96-well plate and exposed to single concentration (25 mg/ml) of different bioactive glass samples (K1, K2, K3, K4 and K5) and incubated at 37 1C, 5% CO 2 , for 18 h. For human PBMC, the cells were incubated with different concentrations of bioactive glass samples and incubated at 37 1C, 5% CO 2 , for 18 h. Optical density (OD) was measured at 450 nm using Synergy HT Multi-Mode Micro-plate Reader BioTek, USA [43]. The data was presented as the percentage of viable cell calculated from the following formula:…”