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Critical Reviews™ in Therapeutic Drug Carrier Systems

Impact factor: 3.040

ISSN Print: 0743-4863
ISSN Online: 2162-660X

Critical Reviews™ in Therapeutic Drug Carrier Systems

DOI: 10.1615/CritRevTherDrugCarrierSyst.v25.i1.10
pages 1-61

Engineered Nanocarriers of Doxorubicin: A Current Update

Rajesh R. Patil
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, University of Mumbai, N.P.Marg, Mumbai 400 019, India
Swati A. Guhagarkar
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, University of Mumbai, N.P.Marg, Mumbai 400 019, India
Padma V. Devarajan
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, University of Mumbai, N.P.Marg, Mumbai 400 019, India

ABSTRACT

Doxorubicin remains the first line of treatment for various cancers ever since its discovery in 1971. Cardiotoxicity and nephrotoxicity associated with unformulated doxorubicin triggered the development of doxorubicin nanocarriers. Although the therapeutic profile of doxorubicin is appreciably improved by entrapping in nanocarriers, they are largely taken up by organs of the reticuloendothelial system. Engineered nanocarriers of doxorubicin refer to carriers modified to escape recognition by reticuloendothelial system and/or functionalized with target specific ligands for selective accumulation at the target site. The first developments in engineered nanocarriers were the stealth carriers. These effectively bypassed the reticuloendothelial system and enhanced the therapeutic profile of doxorubicin by enabling passive accumulation in tumors. Stealth nanocarriers of doxorubicin revealed significant decrease in cardiotoxicity and nephrotoxicity, which led to the approval of liposomal doxorubicin for clinical applications. Success of liposomal doxorubicin was soon dulled by the appearance of newer toxicities like palmar-plantar erythrodysesthesia commonly referred as hand foot syndrome. The search for the “magic bullet” of doxorubicin has further intensified and resulted in design of engineered nanocarriers with high specificity for cancer cells. This review charts the progress from nanocarriers to engineered nanocarriers of doxorubicin, and highlights the current status of engineered nanocarriers of doxorubicin in clinical trials.