一种可生物降解的吸痰贴,用于可持续的经口腔肽输送

IF 10.5 1区 医学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Hanna Krupke , Nicole Zoratto , Lucie Rabut , Daniel Gao , Nevena Paunović , David Klein Cerrejon , Benoit Dehapiot , Jean-Christophe Leroux
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引用次数: 0

摘要

尽管在多肽的全身递送方面取得了相当大的进展,但它们对胃肠道降解的易感性和高分子量限制了其穿过生物屏障的渗透性,仍然是口服给药的障碍。因此,大多数肽疗法依靠注射来达到治疗效果。最近对生物吸力贴片的研究表明,三种肽(去氨加压素、半马鲁肽和特立帕肽)在体内具有积极作用,但用于贴片制造的材料是不可降解的。在这项工作中,引入了一种更可持续的贴片替代品,用可生物降解的聚合物取代以前使用的材料,旨在去除贴片后降解,以减少对环境的影响。采用可伸缩模铸造工艺对合成的和功能化的共聚酯进行了热交联,得到了所需的器件。对各种材料和形状的机械测试确定了性能最佳的聚合物,同时在水介质和模拟废物中都证实了其降解性。使用猪口腔组织的离体模型验证了可生物降解贴片的功能,显示当与化学渗透增强剂结合时,渗透性差的染料的渗透性增强。在比格犬中,与市售片剂相比,semaglutide的生物利用度(4.11 kDa)大大提高,应用时间仅为10 min。此外,与皮下给药相比,该贴片的相对生物利用度为26% %(1.03 kDa)。这项工作强调了用可生物降解的替代品取代硅胶装置的潜力,为通过口腔吸贴输送肽提供了一种更可持续的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A biodegradable suction patch for sustainable transbuccal peptide delivery

A biodegradable suction patch for sustainable transbuccal peptide delivery

A biodegradable suction patch for sustainable transbuccal peptide delivery
Despite considerable advances in the systemic delivery of peptides, their susceptibility to gastrointestinal degradation and high molecular weight, which restricts permeability across biological barriers, remain obstacles to oral administration. As a result, most peptide therapies rely on injections to achieve therapeutic effects. Recent studies on a bioinspired suction patch demonstrated positive effects in vivo with three peptides – desmopressin, semaglutide, and teriparatide – yet materials used for patch fabrication were non-degradable. In this work, a more sustainable patch alternative is introduced by replacing previously used materials with biodegradable polymers, aiming for degradation of the patch after removal to reduce environmental impact. A scalable mold casting process was employed to thermally crosslink synthesized and functionalized copolyesters, yielding the desired devices. Mechanical testing across various materials and shapes identified the best-performing polymer, while its degradation was confirmed in both aqueous medium and simulated waste. An ex vivo model using porcine buccal tissue validated the functionality of biodegradable patches, showing enhanced permeation of a poorly permeable dye when combined with a chemical permeation enhancer. In beagle dogs, the bioavailability of semaglutide (4.11 kDa) was substantially improved compared to the commercially available tablet, with an application time of only 10 min. Additionally, the patch achieved a relative bioavailability of 26% for bremelanotide (1.03 kDa) compared to subcutaneous administration. This work underscores the potential of replacing silicone devices with biodegradable alternatives, providing a more sustainable approach for peptide delivery via the buccal suction patch.
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来源期刊
Journal of Controlled Release
Journal of Controlled Release 医学-化学综合
CiteScore
18.50
自引率
5.60%
发文量
700
审稿时长
39 days
期刊介绍: The Journal of Controlled Release (JCR) proudly serves as the Official Journal of the Controlled Release Society and the Japan Society of Drug Delivery System. Dedicated to the broad field of delivery science and technology, JCR publishes high-quality research articles covering drug delivery systems and all facets of formulations. This includes the physicochemical and biological properties of drugs, design and characterization of dosage forms, release mechanisms, in vivo testing, and formulation research and development across pharmaceutical, diagnostic, agricultural, environmental, cosmetic, and food industries. Priority is given to manuscripts that contribute to the fundamental understanding of principles or demonstrate the advantages of novel technologies in terms of safety and efficacy over current clinical standards. JCR strives to be a leading platform for advancements in delivery science and technology.
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