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

Abstract

<div><p>Background</p><p>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. PCL<sub>63</sub>-b-PNVP<sub>90</sub> 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.</p><p>Methods</p><p>In this study, we have used micelles of amphiphilic PCL<sub>63</sub>-b-PNVP<sub>90</sub> 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.</p><p>Results</p><p>DOX loaded PCL<sub>63</sub>-b-PNVP<sub>90</sub> block copolymer micelles (DOX-PCL<sub>63</sub>-b-PNVP<sub>90</sub>) shows enhanced growth inhibition and cytotoxicity against human (K-562, JE6.1 and Raji) and mice lymphoma cells (Dalton's lymphoma, DL). DOX-PCL<sub>63</sub>-b-PNVP<sub>90</sub> demonstrates higher levels of tumoricidal effect against DOX-resistant tumor cells compared to free DOX. DOX-PCL<sub>63</sub>-b-PNVP<sub>90</sub> 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.</p><p>Conclusion</p><p>Unlike free DOX, DOX-PCL<sub>63</sub>-b-PNVP<sub>90</sub> does not show cytotoxicity against normal cells. DOX-PCL<sub>63</sub>-b-PNVP<sub>90</sub> prolonged the survival of tumor (DL) bearing mice by enhancing the apoptosis of the tumor cells in targeted organs like liver and spleen.</p></div

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