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Critical Reviews™ in Therapeutic Drug Carrier Systems

Impact factor: 5.367

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

Critical Reviews™ in Therapeutic Drug Carrier Systems

DOI: 10.1615/CritRevTherDrugCarrierSyst.2016015926
pages 401-432

Topotecan Liposomes: A Visit from a Molecular to a Therapeutic Platform

Shivani Saraf
Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Central University, Sagar (M.P.), India 470 003
Ankit Jain
Adina Institute of Pharmaceutical Sciences
Pooja Hurkat
Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Central University, Sagar (M.P.), India 470 003
Sanjay Kumar Jain
Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Central University, Sagar (M.P.), India

ABSTRACT

Topotecan (TPT), a potent anticancer camptothecin analog, is well described for the treatment of ovarian cancer, but has also anticancer activity against small-cell and non-small-cell lung cancer, breast cancer, and acute leukemia. Various nanocarriers, including liposomes, have been exploited for targeted delivery of TPT. However, there are a number of challenges with TPT delivery using TPT liposomes (TLs), such as low encapsulation efficiency, physiological pH labile E ring (hydrolysis), accelerated blood clearance, multidrug resistance, and cancer metastases. This review discusses these problems and the means to overcome them, including modification of TLs using zwitterionic poly(carboxybetaine), prolongation in dosing interval (long-term therapy), and modified liposomal encapsulation techniques including active loading methods. We also explore engineered TLs (surface and integral modifications) such as PEGylated TLs, ligand-anchored TLs, and stimuli-sensitive TLs. Further, potential applications, manifestations at the molecular level, patents granted, and preclinical and clinical outlook for TLs are discussed.