Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemical Engineering and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Chemical Engineering and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Curr Opin Pharmacol. 2017 Oct;36:8-13. doi: 10.1016/j.coph.2017.07.003. Epub 2017 Aug 2.
Orally administered devices could enable the systemic uptake of biologic therapeutics by engineering around the physiological barriers present in the gastrointestinal (GI) tract. Such devices aim to shield cargo from degradative enzymes and increase the diffusion rate of medication through the GI mucosa. In order to achieve clinical relevance, these designs must significantly increase systemic drug bioavailability, deliver a clinically relevant dose and remain safe when taken frequently. Such an achievement stands to reduce our dependence on needle injections, potentially increasing patient adherence and reducing needle-associated complications. Here we discuss the physical and chemical constraints imposed by the GI organs and use these to develop a set of boundary conditions on oral device designs for the delivery of macromolecules. We critically examine how device size affects the rate of intestinal obstruction and hinders the loading capacity of poorly soluble protein drugs. We then discuss how current orally administered devices could solve the problem of tissue permeation and conclude that these physical methods stand to provide an efficacious set of alternatives to the classic hypodermic needle.
口服给药装置可以通过绕过胃肠道 (GI) 中存在的生理屏障来实现生物治疗药物的全身吸收。这些装置旨在保护药物不受降解酶的影响，并增加药物通过 GI 黏膜的扩散速度。为了实现临床相关性，这些设计必须显著提高系统药物生物利用度，输送临床相关剂量，并在频繁使用时保持安全。这一成就有望减少我们对针注射的依赖，可能会提高患者的依从性并减少与针相关的并发症。在这里，我们讨论了 GI 器官施加的物理和化学限制，并利用这些限制为大分子的口服给药装置设计制定了一组边界条件。我们批判性地研究了装置尺寸如何影响肠梗阻的速度并阻碍了难溶性蛋白质药物的载药量。然后，我们讨论了目前的口服给药装置如何解决组织渗透问题，并得出结论，这些物理方法为经典的皮下注射针提供了一套有效的替代方法。
