title: Recent advances in drug delivery strategies for improved therapeutic efficacy of gemcitabine.
abstract: Gemcitabine (2',2'-difluoro-2'-deoxycytidine; dFdC) is an efficacious anticancer agent acting against a wide range of solid tumors, including pancreatic, non-small cell lung, bladder, breast, ovarian, thyroid and multiple myelomas. However, short plasma half-life due to metabolism by cytidine deaminase necessitates administration of high dose, which limits its medical applicability. Further, due to its hydrophilic nature, it cannot traverse cell membranes by passive diffusion and, therefore, enters via nucleoside transporters that may lead to drug resistance. To circumvent these limitations, macromolecular prodrugs and nanocarrier-based formulations of Gemcitabine are gaining wide recognition. The nanoformulations based approaches by virtue of their controlled release and targeted delivery have proved to improve bioavailability, increase therapeutic efficacy and reduce adverse effects of the drug. Furthermore, the combination of Gemcitabine with other anticancer agents as well as siRNAs using nanocarriers has also been investigated in order to enhance its therapeutic potential. This review deals with challenges and recent advances in the delivery of Gemcitabine with particular emphasis on macromolecular prodrugs and nanomedicines.
authors.affiliation: Formulation & Drug Delivery Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi 180001, India.
authors.forename: Ravindra Dhar
authors.initials: RD
authors.lastname: Dubey
authors.affiliation: Formulation & Drug Delivery Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi 180001, India.
authors.forename: Ankit
authors.initials: A
authors.lastname: Saneja
authors.affiliation: Natural Product Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi 180001, India. Electronic address: guptap@iiim.res.in.
authors.forename: Prasoon K
authors.initials: PK
authors.lastname: Gupta
authors.affiliation: Formulation & Drug Delivery Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi 180001, India. Electronic address: pngupta@iiim.res.in.
authors.forename: Prem N
authors.initials: PN
authors.lastname: Gupta
mesh_terms: D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Gemcitabine; Nanoparticles; Polymer-drug conjugates; Targeted delivery