Department of Pharmaceutical biotechnology, Urmia University of medical sciences, Urmia, Iran.
J Pharm Pharm Sci. 2019;22(1):37-48. doi: 10.18433/jpps29891.
Epidermal growth factor receptors (EGFRs) have potential to be considered as therapeutic target for cancer treatment especially in cancer patients with overexpression of EGFR. Cetuximab as a first monoclonal antibody and Imatinib as the first small molecule tyrosine kinase inhibitor (SMTKI) were approved by FDA in 1998 and 2001. About 28 SMTKIs have been approved until 2015 and a large number of compound with kinase inhibitory activity are at the different phases of clinical trials. Although Kinase inhibitors target specific intracellular pathways, their tissue or cellular distribution are not specific. So treatment with these drugs causes serious dose dependent side effects. Targeted delivery of kinase inhibitors via dendrimers, polymeric nanoparticles, magnetic nanoparticles and lipid based delivery systems such as liposomes, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) can lead to reduction of side effects and improving therapeutic efficacy of the drugs in the target organs. Furthermore formulation of these drugs is challenged by their physicochemical properties such as solubility and dissolution rate. The main approaches in order to increase dissolution rate, are particle size reduction, self-emulsification, cyclodextrin complexation, crystal modification and amorphous solid dispersion. Synergistic therapeutic effect, decreased side effects and drug resistant, reduced cost and increased patient compliance are the advantages associated with using combination therapy especially in the treatment of cancer. Combination of TKIs with chemotherapeutic agents or biopharmaceuticals such as monoclonal antibodies and oligonucleotides and also combination of two TKIs within one formulation is possible by new targeting delivery systems. This article reviews the recent advances in the design and development of delivery systems for TKIs.
表皮生长因子受体（EGFRs）有可能被视为癌症治疗的治疗靶点，尤其是在 EGFR 过度表达的癌症患者中。西妥昔单抗是第一个单克隆抗体，伊马替尼是第一个小分子酪氨酸激酶抑制剂（SMTKI），于 1998 年和 2001 年获得 FDA 批准。截至 2015 年，已有约 28 种 SMTKI 获得批准，还有大量具有激酶抑制活性的化合物处于不同的临床试验阶段。尽管激酶抑制剂针对特定的细胞内途径，但它们的组织或细胞分布并不具有特异性。因此，这些药物的治疗会导致严重的剂量依赖性副作用。通过树枝状大分子、聚合物纳米粒子、磁性纳米粒子和基于脂质的递药系统（如脂质体、固体脂质纳米粒（SLN）和纳米结构脂质载体（NLC））对激酶抑制剂进行靶向递药，可导致副作用减少，并提高药物在靶器官中的治疗效果。此外，这些药物的制剂还受到其物理化学性质（如溶解度和溶出速率）的挑战。为了提高溶出速率，主要方法有减小粒径、自乳化、环糊精包合、晶体修饰和无定形固体分散体。联合治疗的优点包括协同治疗效果、降低副作用和耐药性、降低成本和提高患者依从性，特别是在癌症治疗中。通过新的靶向递药系统，将 TKI 与化疗药物或生物药物（如单克隆抗体和寡核苷酸）联合使用，或将两种 TKI 联合在一个制剂中使用，都是可能的。本文综述了 TKI 递药系统设计和开发的最新进展。
