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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.2017017912
pages 63-96

Lessons Learned from Gemcitabine: Impact of Therapeutic Carrier Systems and Gemcitabine’s Drug Conjugates on Cancer Therapy

Sathish Dyawanapelly
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Raebareli, 229 010, India
Animesh Kumar
Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, 226 013, India
Manish K. Chourasia
Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, 226 013, India

ABSTRACT

Currently, drug delivery systems have a high impact in cancer therapy and are receiving more attention than conventional cancer treatment modalities. Compared with current cancer therapies, gemcitabine (2', 2'-difluoro-2'-deoxycytidine) has been proven to be an effective chemotherapeutic agent against pancreatic, colon, bladder, breast, ovarian, non-small-cell lung, and head and neck cancers in combination with other anticancer agents. To improve the safety and efficacy of cytotoxic drugs, several drug delivery systems have been explored. This review outlines the recent work directed toward gemcitabine delivery systems for cancer therapy, including aerosols, polymeric nanoparticles, liposomes, microparticles, carbon nanotubes, and multifunctional theranostic nanomedicines. It also provides insight into the design and development of gemcitabine conjugation for safe and effective cancer therapy. Despite the clinical promises of gemcitabine, many therapeutic challenges remain. Specifically, its therapeutic use in cancer chemotherapy is impeded by a short biological half-life, caused by its rapid metabolism, and resistance due to increased expression of ribonucleotide reductase. In our opinion, many research investigations have contributed to improve the selectivity and efficacy of gemcitabine. This combined approach of drug delivery systems and gemcitabine conjugates has shown promising efficacy in preclinical models and significant potential for future clinical cancer-therapeutic applications. Also, these strategies overcome most of the aforementioned limits of gemcitabine.