Targeted delivery of doxorubicin-loaded poly (ε-caprolactone)-b-poly (N-vinylpyrrolidone) micelles enhances antitumor effect in lymphoma.

Abstract

The 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.In 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.DOX 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.Unlike 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.