抗癌药物长效药物输送系统的最新进展
Recent advances in long-acting drug delivery systems for anticancer drug
影响因子:17.60000
分区:医学1区 Top / 药学1区
发表日期:2023 Mar
作者:
Catarina Pacheco, Ana Baião, Tao Ding, Wenguo Cui, Bruno Sarmento
摘要
全身性抗癌化疗的使用在本质上受到其毒性的限制。无论是处理小分子还是生物药物，在全身给药后，小剂量都无法达到有效的肿瘤内浓度，而高剂量的高剂量具有明显的肿瘤抑制作用，也可能促使健康细胞死亡，危害患者。因此，已经设计了基于药物输送系统（DDSS）的策略。由于它们有能力保护药物免受早期消除和控制药物释放的侵害，DDS可以通过将其循环时间或稳步释放到肿瘤部位来促进肿瘤暴露于抗癌治疗剂中。然而，由于安全性，还需要通过操纵其物理化学特征来改善量身定制的DDSS系统用于临床使用的批准。在过去的几年中，已经描述了几种策略，以提高其安全性，稳定性和微调药物释放动力学。本文中，我们回顾了主要的DDS，即聚合物缀合物，纳米或微粒，水凝胶和微针，探索了用于长效抗癌治疗的探索，重点介绍了最近提出的修饰及其对不同抗癌疗法的潜在优势。此外，还涵盖了长效抗癌疗法和未来技术方向的重要局限性。
Abstract
The use of systemic anticancer chemotherapy is intrinsically limited by its toxicity. Whether dealing with small molecules or biopharmaceuticals, after systemic administration, small doses fail to reach effective intratumoral concentrations, while high doses with significant tumor inhibition effects may also drive the death of healthy cells, endangering the patients. Therefore, strategies based on drug delivery systems (DDSs) for avoiding the systemic toxicity have been designed. Due to their ability to protect drugs from early elimination and control drug release, DDSs can foster tumor exposure to anticancer therapeutics by extending their circulation time or steadily releasing drugs into the tumor sites. However, approval of tailored DDSs systems for clinical use is minimal as the safety and the in vivo activity still need to be ameliorated by manipulating their physicochemical characteristics. During the last few years, several strategies have been described to improve their safety, stability, and fine-tune pharmaceuticals release kinetics. Herein, we reviewed the main DDSs, namely polymeric conjugates, nano or microparticles, hydrogels, and microneedles, explored for long-acting anticancer treatments, highlighting recently proposed modifications and their potential advantages for different anticancer therapies. Additionally, important limitations of long-acting anticancer therapies and future technology directions were also covered.