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用于不稳定分子皮内药物控释的多隔室可生物降解聚合物微针的无创生产

Non-invasive Production of Multi-Compartmental Biodegradable Polymer Microneedles for Controlled Intradermal Drug Release of Labile Molecules.

作者信息

Battisti Mario, Vecchione Raffaele, Casale Costantino, Pennacchio Fabrizio A, Lettera Vincenzo, Jamaledin Rezvan, Profeta Martina, Di Natale Concetta, Imparato Giorgia, Urciuolo Francesco, Netti Paolo Antonio

机构信息

Center for Advanced Biomaterials for Health Care (CABHC), Istituto Italiano di Tecnologia, Naples, Italy.

Interdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, Naples, Italy.

出版信息

Front Bioeng Biotechnol. 2019 Nov 8;7:296. doi: 10.3389/fbioe.2019.00296. eCollection 2019.

Abstract

Transdermal drug delivery represents an appealing alternative to conventional drug administration systems. In fact, due to their high patient compliance, the development of dissolvable and biodegradable polymer microneedles has recently attracted great attention. Although stamp-based procedures guarantee high tip resolution and reproducibility, they have long processing times, low levels of system engineering, are a source of possible contaminants, and thermo-sensitive drugs cannot be used in conjunction with them. In this work, a novel stamp-based microneedle fabrication method is proposed. It provides a rapid room-temperature production of multi-compartmental biodegradable polymeric microneedles for controlled intradermal drug release. Solvent casting was carried out for only a few minutes and produced a short dissolvable tip made of polyvinylpyrrolidone (PVP). The rest of the stamp was then filled with degradable poly(lactide-co-glycolide) (PLGA) microparticles (μPs) quickly compacted with a vapor-assisted plasticization. The outcome was an array of microneedles with tunable release. The ability of the resulting microneedles to indent was assessed using pig cadaver skin. Controlled intradermal delivery was demonstrated by loading both the tip and the body of the microneedles with model therapeutics; POXA1b laccase from is a commercial enzyme used for the whitening of skin spots. The action and indentation of the enzyme-loaded microneedle action were assessed in an skin model and this highlighted their ability to control the kinetic release of the encapsulated compound.

摘要

经皮给药是传统给药系统颇具吸引力的替代方案。事实上,由于患者依从性高,可溶解且可生物降解的聚合物微针的研发近来备受关注。尽管基于印章的制作方法能保证高针尖分辨率和可重复性,但它们加工时间长、系统工程水平低、可能产生污染物,且热敏药物不能与之配合使用。在这项工作中,提出了一种新颖的基于印章的微针制造方法。它能在室温下快速生产用于控制皮内药物释放的多隔室可生物降解聚合物微针。溶剂浇铸仅需几分钟,就能制造出由聚乙烯吡咯烷酮(PVP)制成的短可溶解针尖。然后,印章的其余部分填充可降解的聚(丙交酯 - 乙交酯)(PLGA)微粒(μPs),通过蒸汽辅助塑化快速压实。结果得到了一系列具有可调释性的微针。使用猪尸体皮肤评估了所得微针的刺入能力。通过在微针的针尖和主体中加载模型治疗剂来证明可控的皮内给药;来自的POXA1b漆酶是一种用于美白色斑的商业酶。在皮肤模型中评估了载酶微针的作用和刺入情况,这突出了它们控制封装化合物动力学释放的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/479e/6856554/224843d28734/fbioe-07-00296-g0008.jpg

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