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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Immunobiology Laboratory, Department of Zoology, Faculty of Science, Banaras Hindu University, Varanasi, India.
Sumit Kumar
SK
Hira
Department of Chemistry, Faculty of Science, Banaras Hindu University, Varanasi, India.
Avnish Kumar
AK
Mishra
Department of Chemistry, Faculty of Science, Banaras Hindu University, Varanasi, India.
Biswajit
B
Ray
Immunobiology Laboratory, Department of Zoology, Faculty of Science, Banaras Hindu University, Varanasi, India.
Partha Pratim
PP
Manna
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002208:Caproates / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007783:Lactones / Q000737:chemistry*; D008223:Lymphoma / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011760:Pyrrolidinones / Q000737:chemistry*; D047368:Tumor Burden / Q000187:drug effects; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; D002208:Caproates; D004337:Drug Carriers; D007783:Lactones; D008823:Micelles; D011108:Polymers; D011760:Pyrrolidinones; C121056:caprolactone; C042670:N-vinyl-2-pyrrolidinone; D004317:Doxorubicin