Dyawanapelly Sathish, Kumar Animesh, Chourasia Manish K
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Raebareli, 229 010, India.
Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, 226 013, India.
Crit Rev Ther Drug Carrier Syst. 2017;34(1):63-96. doi: 10.1615/CritRevTherDrugCarrierSyst.2017017912.
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.
目前，药物递送系统在癌症治疗中具有重大影响，并且比传统癌症治疗方式受到更多关注。与当前的癌症治疗方法相比，吉西他滨（2'，2'-二氟-2'-脱氧胞苷）已被证明是一种有效的化疗药物，可与其他抗癌药物联合用于治疗胰腺癌、结肠癌、膀胱癌、乳腺癌、卵巢癌、非小细胞肺癌以及头颈癌。为了提高细胞毒性药物的安全性和有效性，人们探索了多种药物递送系统。本综述概述了近期针对用于癌症治疗的吉西他滨递送系统所开展的工作，包括气雾剂、聚合物纳米颗粒、脂质体、微粒、碳纳米管以及多功能诊疗纳米药物。它还深入探讨了用于安全有效的癌症治疗的吉西他滨缀合物的设计与开发。尽管吉西他滨具有临床应用前景，但仍存在许多治疗挑战。具体而言，其在癌症化疗中的治疗应用受到快速代谢导致的较短生物半衰期以及核糖核苷酸还原酶表达增加引起的耐药性的阻碍。我们认为，许多研究调查有助于提高吉西他滨的选择性和疗效。药物递送系统与吉西他滨缀合物的这种联合方法在临床前模型中已显示出有前景的疗效，并且在未来临床癌症治疗应用中具有巨大潜力。此外，这些策略克服了上述吉西他滨的大多数局限性。
