In Vivo Anticancer Efficacy and Toxicity Studies of a Novel Polymer Conjugate N-Acetyl Glucosamine (NAG)-PEG-Doxorubicin for Targeted Cancer Therapy

AAPS PharmSciTech
Smita K PawarPradeep Vavia

Abstract

A novel polymer-drug conjugate, polyethylene glycol-N-(acetyl)-glucosamine-doxorubicin (PEG-NAG-DOX) was evaluated in this study for its in vivo potential for treatment of tumours demonstrating improved efficacy and reduced toxicity. The proposed polymer-drug conjugate comprised of polyethylene glycol-maleimide (mPEG-MAL, 30000 Da) as a carrier, doxorubicin (DOX) as an anticancer drug and N-acetyl glucosamine (NAG) as a targeting moiety as well as penetration enhancer. Doxorubicin has a potent and promising anticancer activity; however, severe cardiotoxicity limits its application in cancer treatment. By modifying DOX in PEG-NAG-DOX prodrug conjugate, we aimed to eliminate this limitation. In vivo anticancer efficacy of the conjugate was evaluated using BDF mice-induced skin melanoma model by i.v. administration of DOX conjugates. Anticancer efficacy studies were done by comparing tumour volume, body weight, organ index and percent survival rate of the animals. Tumour suppression achieved by PEG-NAG-DOX at the cumulative dose of 7.5 mg/kg was two-fold better than that achieved by DOX solution. Also, the survival rate for PEG-NAG-DOX conjugate was >70% as compared to <50% survival rate for DOX solution. In addition, toxicity stu...Continue Reading

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Citations

Mar 14, 2019·Current Pharmaceutical Design·Felipe Dos Santos ArrudaMara Rúbia Nunes Celes
Sep 10, 2019·Therapeutic Delivery·Vahid Taghipour-SabzevarMehrdad Moosazadeh Moghaddam
Sep 20, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Fatemeh ZahedipourKhadijeh Jamialahmadi

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Methods Mentioned

BETA
light microscopy
Assay
MDA
NMR
dynamic light scattering

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