Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands; Biological Research Pharmacology Department, Sun Pharma Advanced Research Company Ltd, India.
Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
J Control Release. 2018 Oct 10;287:194-215. doi: 10.1016/j.jconrel.2018.08.034. Epub 2018 Aug 28.
Hematological malignancies (HM) are a collection of malignant transformations originating from cells in the primary or secondary lymphoid organs. Leukemia, lymphoma, and multiple myeloma comprise the three major types of HM. Current treatment consists of bone marrow transplantation, radiotherapy, immunotherapy and chemotherapy. Although, many chemotherapeutic drugs are clinically available for the treatment of HM, the use of these agents is limited due to dose-related toxicity and lack of specificity to tumor tissue. Moreover, the poor pharmacokinetic profile of most of the chemotherapeutics requires high dosage and frequent administration to maintain therapeutic levels at the target site, both increasing adverse effects. This underlines an urgent need for a suitable drug delivery system to improve efficacy, safety, and pharmacokinetic properties of conventional therapeutics. Nanomedicines have proven to enhance these properties for anticancer therapeutics. The most extensively studied nanomedicine systems are lipid-based nanoparticles and polymeric nanoparticles. Typically, nanomedicines are small sub-micron sized particles in the size range of 20-200 nm. The biocompatible and biodegradable nature of nanomedicines makes them attractive vehicles to improve drug delivery. Their small size allows them to extravasate and accumulate at malignant sites passively by means of the enhanced permeability and retention (EPR) effect, resulting from rapid angiogenesis and inflammation. Moreover, the specificity to the target tissue can be further enhanced by surface modification of nanoparticles. This review describes currently available therapies as well as limitations and potential advantages of nanomedicine formulations for treatment of various types of HM. Additionally, recent investigational and approved nanomedicine formulations and their limited applications in HM are discussed.
血液系统恶性肿瘤（HM）是一组起源于初级或次级淋巴器官细胞的恶性转化。白血病、淋巴瘤和多发性骨髓瘤构成了 HM 的三种主要类型。目前的治疗方法包括骨髓移植、放疗、免疫疗法和化疗。尽管有许多化疗药物可用于治疗 HM，但由于与剂量相关的毒性和对肿瘤组织缺乏特异性，这些药物的应用受到限制。此外，大多数化疗药物的药代动力学特征不佳，需要高剂量和频繁给药才能在靶位维持治疗水平，这两者都会增加不良反应。这凸显了迫切需要一种合适的药物输送系统来提高常规治疗的疗效、安全性和药代动力学特性。纳米医学已被证明可增强抗癌治疗的这些特性。研究最多的纳米医学系统是基于脂质的纳米颗粒和聚合物纳米颗粒。通常，纳米药物是亚微米大小的小颗粒，尺寸范围在 20-200nm 之间。纳米药物的生物相容性和可生物降解性使其成为改善药物输送的有吸引力的载体。它们的小尺寸使它们能够通过快速血管生成和炎症导致的增强的通透性和保留（EPR）效应被动地渗出并在恶性部位积累。此外，通过纳米颗粒的表面修饰可以进一步增强对靶组织的特异性。本综述描述了目前可用的治疗方法以及纳米医学制剂在治疗各种类型 HM 中的局限性和潜在优势。此外，还讨论了最近的研究性和批准的纳米医学制剂及其在 HM 中的有限应用。
