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基于聚合物的纳米颗粒作为医学上已确立重要性的嘌呤类药物递送系统。

Polymer-Based Nanoparticles as Drug Delivery Systems for Purines of Established Importance in Medicine.

作者信息

Szyk Piotr, Czarczynska-Goslinska Beata, Mlynarczyk Dariusz T, Ślusarska Barbara, Kocki Tomasz, Ziegler-Borowska Marta, Goslinski Tomasz

机构信息

Chair and Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznań, Poland.

Chair and Department of Pharmaceutical Technology, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznań, Poland.

出版信息

Nanomaterials (Basel). 2023 Sep 26;13(19):2647. doi: 10.3390/nano13192647.

Abstract

Many purine derivatives are active pharmaceutical ingredients of significant importance in the therapy of autoimmune diseases, cancers, and viral infections. In many cases, their medical use is limited due to unfavorable physicochemical and pharmacokinetic properties. These problems can be overcome by the preparation of the prodrugs of purines or by combining these compounds with nanoparticles. Herein, we aim to review the scientific progress and perspectives for polymer-based nanoparticles as drug delivery systems for purines. Polymeric nanoparticles turned out to have the potential to augment antiviral and antiproliferative effects of purine derivatives by specific binding to receptors (ASGR1-liver, macrophage mannose receptor), increase in drug retention (in eye, intestines, and vagina), and permeation (intranasal to brain delivery, PEPT1 transport of acyclovir). The most significant achievements of polymer-based nanoparticles as drug delivery systems for purines were found for tenofovir disoproxil in protection against HIV, for acyclovir against HSV, for 6-mercaptopurine in prolongation of mice ALL model life, as well as for 6-thioguanine for increased efficacy of adoptively transferred T cells. Moreover, nanocarriers were able to diminish the toxic effects of acyclovir, didanosine, cladribine, tenofovir, 6-mercaptopurine, and 6-thioguanine.

摘要

许多嘌呤衍生物是治疗自身免疫性疾病、癌症和病毒感染的重要活性药物成分。在许多情况下,由于其不利的物理化学和药代动力学性质,它们的医学应用受到限制。这些问题可以通过制备嘌呤前药或将这些化合物与纳米颗粒结合来克服。在此,我们旨在综述基于聚合物的纳米颗粒作为嘌呤药物递送系统的科学进展和前景。结果表明,聚合物纳米颗粒有可能通过与受体(ASGR1-肝脏、巨噬细胞甘露糖受体)特异性结合来增强嘌呤衍生物的抗病毒和抗增殖作用,增加药物在眼部、肠道和阴道的滞留,并促进药物渗透(鼻内给药至脑递送、阿昔洛韦的PEPT1转运)。作为嘌呤药物递送系统,基于聚合物的纳米颗粒最显著的成果体现在替诺福韦酯对HIV的防护、阿昔洛韦对HSV的防护、6-巯基嘌呤对小鼠急性淋巴细胞白血病模型生存期的延长,以及6-硫鸟嘌呤对过继转移T细胞疗效的提高。此外,纳米载体能够减轻阿昔洛韦、去羟肌苷、克拉屈滨、替诺福韦、6-巯基嘌呤和6-硫鸟嘌呤的毒性作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28e3/10574807/145e76dc3cb2/nanomaterials-13-02647-g001.jpg

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