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近年来,抗癌药物长效药物传递系统的研究进展。

Recent advances in long-acting drug delivery systems for anticancer drug.

机构信息

i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; IUCS - Instituto Universitário de Ciências da Saúde, CESPU, Rua Central de Gandra 1317, 4585-116 Gandra, Portugal.

i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.

出版信息

Adv Drug Deliv Rev. 2023 Mar;194:114724. doi: 10.1016/j.addr.2023.114724. Epub 2023 Feb 4.

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.

摘要

全身化疗的应用受到其毒性的内在限制。无论是处理小分子还是生物制药,全身给药后,小剂量无法达到有效的肿瘤内浓度,而具有显著肿瘤抑制作用的高剂量也可能导致健康细胞死亡,危及患者。因此,设计了基于药物传递系统(DDS)的策略来避免全身毒性。由于其能够保护药物免受早期消除并控制药物释放的能力,DDS 可以通过延长药物循环时间或向肿瘤部位稳定释放药物来促进肿瘤暴露于抗癌治疗药物。然而,由于需要通过操纵其物理化学特性来改善其安全性和体内活性,定制的 DDS 系统用于临床应用的批准很少。在过去的几年中,已经描述了几种策略来提高其安全性、稳定性和微调药物释放动力学。本文综述了用于长效抗癌治疗的主要 DDS,即聚合物缀合物、纳米或微粒、水凝胶和微针,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,还涵盖了长效抗癌治疗的重要局限性和未来技术方向。

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