Science Focus (issue 24)

試想像如果你需要每週七天,每天四次在腹部進行注 射,你會感到害怕嗎?這正是第一型糖尿病患者所面對的困 境 [1]。由於身體無法產生足夠胰島素,這些患者需要通過 定期注射來降低血糖水平。 為了幫助第一型糖尿病患者,科學家和醫生幾十年來都 在尋找可靠的口服胰島素系統,可是極端 pH 值、蛋白酶以 及消化道的厚黏液層都為相關研究帶來巨大挑戰。 在 2019 年,麻省理工學院的研究人員發表了一項突 破性研究,他們設計了一種只有一顆藍莓大小,名為自我 定向毫米級投藥器(self-orienting millimeter-scale applicator,簡稱SOMA)的可服用裝置 [2, 3]。SOMA 麻雀雖小,但設計卻非常精巧 — 它是一顆包含隱藏針頭, 一與胃壁接觸就會注射胰島素的膠囊。讓我們仔細看看 SOMA 沿著消化道充滿挑戰但又成功的旅程吧! 患者吞服SOMA後,膠囊會沿食道進入胃部。 SOMA 第一步會自動將其注射裝置指向胃壁。這個巧妙 的自動導向系統靈感來自看似風馬牛不相及的豹紋陸龜 (Stigmochelys paradali),這種陸龜的低重心和陡峭的 圓拱形外殼使它始終能夠回到直立的狀態。研究人員以電 腦模型優化 SOMA的拱形,並用低密度聚己內酯和高密度 不銹鋼兩者的組合來降低重心。實驗結果顯示 SOMA 只需 一秒鐘就能自動導向。 Thinking Out of the Box Oral Insulin Pill article. Please rest assured that patients would not feel any pain as the stomach wall has no pain receptors. The effectiveness of stomach wall injection by SOMA was also proved to be comparable to conventional subcutaneous injection in pig studies. In fact, insulin is just one of the many drugs that could potentially be delivered by SOMA. To improve the applicability of SOMA, the team reported a new version of SOMA in 2021, the liquid-injecting SOMA (L-SOMA). It could deliver monoclonal antibodies in liquid form and at larger dosing volumes [4], implying that it could potentially target cancers and autoimmune diseases (e.g. rheumatoid arthritis) besides diabetes. The scope of applicable biomacromolecules further expanded to RNA in early 2022 [5, 6]. As single-stranded RNA is susceptible to degradation, researchers made use of protective polymeric nanoparticles to produce RNA-nanoparticle complexes. Results showed that SOMA was able to deliver these complexes into stomach cells at an amount comparable to that in COVID-19 vaccines. We are a step closer to oral mRNA vaccines now!