An ingestible self-orienting system for oral delivery of macromolecules

Abstract

Biomacromolecules have transformed our capacity to effectively treat diseases; however, their rapid degradation and poor absorption in the gastrointestinal (GI) tract generally limit their administration to parenteral routes. An oral biologic delivery system must aid in both localization and permeation to achieve systemic drug uptake. Inspired by the leopard tortoise’s ability to passively reorient, we developed an ingestible self-orienting millimeter-scale applicator (SOMA) that autonomously positions itself to engage with GI tissue. It then deploys milliposts fabricated from active pharmaceutical ingredients directly through the gastric mucosa while avoiding perforation. We conducted in vivo studies in rats and swine that support the applicator’s safety and, using insulin as a model drug, demonstrated that the SOMA delivers active pharmaceutical ingredient plasma levels comparable to those achieved with subcutaneous millipost administration.

A Proresolving Peptide Nanotherapy for Site‐Specific Treatment of Inflammatory Bowel Disease by Regulating Proinflammatory Microenvironment and Gut Microbiota

“…[13,14] A recent study revealed the potential of Ac2-26 for the treatment of colitis after intraperitoneal or intramucosal injection of Ac2-26 in nanoparticles (NPs). [16][17][18][19][20][21] However, there are still tremendous challenges in the design and development of translational nanovehicles for oral delivery of macromolecular therapeutics, [16,[22][23][24][25] although different nanotherapies have been developed for targeted treatment of IBD. On the other hand, patient-friendly oral delivery is highly preferred for treatment of gastrointestinal and chronic diseases, owing to its convenience, high patient compliance, desirable cost-effectiveness, and good safety profile.…”

Role of Tissue Engineering in COVID-19 and Future Viral Outbreaks

“…These allowed for insulin delivery in a porcine model and may facilitate oral delivery of medications previously only efficacious in intravenous form. 53 Lastly, short interfering RNA (siRNA) has also been explored as both prophylaxis and therapy for coronavirus infection. 54 For sequences specific to SARS-CoV-1, siRNA was effective in a NHP model, 39 resulting in diminished viral load and alveolar damage.…”

Immunology‐Guided Biomaterial Design for Mucosal Cancer Vaccines

“…C) Oral delivery devices including microneedle‐based devices that directly penetrate the gastric mucosa (i) and the intestinal mucosa (ii), hydrogels, scaffolds, and NPs/MPs. i) Reproduced with permission . Copyright 2019, The Authors, published by AAAS.…”

“…Alternatively, microneedles may be designed to deliver proteins directly to mucosal surfaces, via rectal application of a patch or using ingestible devices, that autonomously inserts payload into the GI mucosa . In one example, the device, composed of PCL and stainless steel, was shaped as mono‐monostatic body, with a shifted center of mass and a high‐curvature upper shell . The shape feature enables it to align itself with the tissue of the GI tract and deploy a microneedle (Figure Ci).…”

“…Thus, it should be chosen when other delivery routes are indisposed. In that case, in addition to particulate‐based vaccine and scaffolds, oral delivery can be used, for example with ingestible microneedle‐based devices . While protection from pH and enzymatic degradation is a key consideration for all delivery routes, it is of particular importance when the vaccination platform passes through the GI.…”