新型微針注射器可用於口服遞送大分子
作者：
小柯機器人發布時間：2019/10/9 11:07:18
美國麻省理工學院Giovanni Traverso和Robert Langer等研究人員合作開發了可用於大分子口服遞送的腔內展開微針注射器。2019年10月7日，《自然—醫學》在線發表了這項成果。
研究人員開發了一種稱為腔內展開微針注射器的可吸收膠囊，其通過使用一組展開臂將可溶解藥物的微針快速推進腸道組織，從而可以口服遞送生物藥物。在人體外和豬體內的研究表明，該設備始終將微針遞送至組織，而不會引起完全的厚度穿孔。使用胰島素作為模型藥物，研究人員發現，當膠囊啟動時，管腔展開微針注射器在4小時的採樣時間內提供了較快的藥代動力學吸收曲線，並且其皮下注射的系統吸收率比皮下注射高出10％。因為具有裝載多種微針配方的能力，該設備可以用作口服治療劑量的大分子藥物平臺。
研究人員表示，胰島素和其他可注射生物藥物已經改變了對患糖尿病患者的治療，但是患者和醫療保健提供者通常更喜歡使用並開出口服效果不佳的藥物。與皮下給藥的藥物相比，口服製劑可減少患者不適，在高溫下顯示出更高的化學穩定性，並且不會產生生物危害性的針頭廢物。生物藥物的口服劑型是理想的。但是，大分子藥物不易通過胃腸道吸收到血液中。
附：英文原文
Title: A luminal unfolding microneedle injector for oral delivery of macromolecules
Author: Alex Abramson, Ester Caffarel-Salvador, Vance Soares, Daniel Minahan, Ryan Yu Tian, Xiaoya Lu, David Dellal, Yuan Gao, Soyoung Kim, Jacob Wainer, Joy Collins, Siddartha Tamang, Alison Hayward, Tadayuki Yoshitake, Hsiang-Chieh Lee, James Fujimoto, Johannes Fels, Morten Revsgaard Frederiksen, Ulrik Rahbek, Niclas Roxhed, Robert Langer, Giovanni Traverso
Issue&Volume: 2019-10-07
Abstract: Insulin and other injectable biologic drugs have transformed the treatment of patients suffering from diabetes1,2, yet patients and healthcare providers often prefer to use and prescribe less effective orally dosed medications35. Compared with subcutaneously administered drugs, oral formulations create less patient discomfort4, show greater chemical stability at high temperatures6, and do not generate biohazardous needle waste7. An oral dosage form for biologic medications is ideal; however, macromolecule drugs are not readily absorbed into the bloodstream through the gastrointestinal tract8. We developed an ingestible capsule, termed the luminal unfolding microneedle injector, which allows for the oral delivery of biologic drugs by rapidly propelling dissolvable drug-loaded microneedles into intestinal tissue using a set of unfolding arms. During ex vivo human and in vivo swine studies, the device consistently delivered the microneedles to the tissue without causing complete thickness perforations. Using insulin as a model drug, we showed that, when actuated, the luminal unfolding microneedle injector provided a faster pharmacokinetic uptake profile and a systemic uptake >10% of that of a subcutaneous injection over a 4-h sampling period. With the ability to load a multitude of microneedle formulations, the device can serve as a platform to orally deliver therapeutic doses of macromolecule drugs. A luminal unfolding microneedle injector device (LUMI) is engineered as a custom capsule capable of efficient biologic macromolecular drug delivery into the bloodstream via selective deployment within the gastrointestinal tract.
DOI: 10.1038/s41591-019-0598-9
Source:https://www.nature.com/articles/s41591-019-0598-9