当前位置: X-MOL 学术Glycobiology › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Heparosan-Coated Liposomes for Drug Delivery
Glycobiology ( IF 3.4 ) Pub Date : 2017-08-10 , DOI: 10.1093/glycob/cwx070
Rachel S Lane 1 , F Michael Haller 2 , Anais A E Chavaroche 2 , Andrew Almond 3 , Paul L DeAngelis 1, 2
Affiliation  

Liposomal encapsulation is a useful drug delivery strategy for small molecules, especially chemotherapeutic agents such as doxorubicin. Doxil® is a doxorubicin-containing liposome (“dox-liposome”) that passively targets drug to tumors while reducing side effects caused by free drug permeating and poisoning healthy tissues. Polyethylene glycol (PEG) is the hydrophilic coating of Doxil® that protects the formulation from triggering the mononuclear phagocyte system (MPS). Evading the MPS prolongs dox-liposome circulation time thus increasing drug deposition at the tumor site. However, multiple doses of Doxil® sometimes activate an anti-PEG immune response that enhances liposome clearance from circulation and causes hypersensitivity, further limiting its effectiveness against disease. These side effects constrain the utility of PEG-coated liposomes in certain populations, justifying the need for investigation into alternative coatings that could improve drug delivery for better patient quality of life and outcome. We hypothesized that heparosan (HEP; [-4-GlcA-β1-4-GlcNAc-α1-]n) may serve as a PEG alternative for coating liposomes. HEP is a natural precursor to heparin biosynthesis in mammals. Also, bacteria expressing an HEP extracellular capsule during infection escape detection and are recognized as “self,” not a foreign threat. By analogy, coating drug-carrying liposomes with HEP should camouflage the delivery vehicle from the MPS, extending circulation time and potentially avoiding immune-mediated clearance. In this study, we characterize the postmodification insertion of HEP-lipids into liposomes by dynamic light scattering and coarse-grain computer modeling, test HEP-lipid immunogenicity in rats, and compare the efficacy of drug delivered by HEP-coated liposomes to PEG-coated liposomes in a human breast cancer xenograft mouse model.

中文翻译:

肝素包衣的脂质体用于药物递送

脂质体包封是用于小分子,尤其是化学治疗剂如阿霉素的有用的药物递送策略。阿霉素®是含多柔比星脂质体(“DOX的脂质体”),该被动目标药物到肿瘤,同时减少由游离药物渗透和中毒健康组织的副作用。聚乙二醇(PEG)是阿霉素的亲水性涂层®保护制剂从触发单核吞噬细胞系统(MPS)。避免MPS延长了Dox-脂质体的循环时间,从而增加了在肿瘤部位的药物沉积。然而,多剂量阿霉素的®有时会激活抗PEG免疫反应,从而增强脂质体从循环中的清除并引起超敏反应,从而进一步限制了其抗疾病的功效。这些副作用限制了PEG包被的脂质体在某些人群中的应用,证明有必要研究替代涂层以改善药物递送以改善患者的生活质量和结局。我们假设肝素(HEP; [-4-GlcA-β1-4-GlcNAc-α1-] n)可用作包衣脂质体的PEG替代品。HEP是哺乳动物肝素生物合成的天然前体。此外,在感染过程中表达HEP细胞外囊的细菌会逃脱检测,并被认为是“自身”,而不是外来威胁。以此类推,用HEP包裹载药脂质体应能掩盖MPS中的递送载体,延长循环时间并可能避免免疫介导的清除。在这项研究中,我们通过动态光散射和粗粒计算机建模表征了HEP-脂质在修饰后插入脂质体中的功能,测试了大鼠的HEP-脂质免疫原性,并比较了HEP-涂层脂质体向PEG-涂层中递送药物的功效人乳腺癌异种移植小鼠模型中的脂质体。
更新日期:2017-09-08
down
wechat
bug