for inflammatory bowel disease (IBD) is primarily achieved through oral or intravenous delivery of therapeutic agents. [4,5] A wide variety of drugs can be employed, including aminosalicylic acids, corticosteroids, immunosuppressants, and various biological macromolecules. [6][7][8] These medications have a myriad of adverse side effects, limiting the course of treatment for patients. [9][10][11] For example, corticosteroid treatment duration is limited to approximately 3 months to mitigate the potential for conditions like osteoporosis, [12,13] and immunosuppressants increase susceptibility to opportunistic infections. [14] The presence of substantial side effects can be partly attributed to the large systemic doses needed to achieve effective therapeutic concentrations within the GI tract. Localizing treatment to inflammatory lesions using topically active agents, like corticosteroids, is one method to reduce the necessary drug dose and combat the adverse systemic side effects associated with intravenous and oral non-site-specific therapeutic delivery. [13,[15][16][17] Highly localized topical treatment may also offer a path to mitigate drug costs by reduced dosing, making room for costs associated with innovative delivery modalities.Commercial technologies exist that can improve the localization of drug release within the GI tract. One such technology is pH-sensitive enteric coatings, like Evonik Eudragit L100, Currentsystemic therapies for inflammatory gastrointestinal (GI) disorders are unable to locally target lesions and have substantial systemic side effects. Here, a compact mesoscale spring actuator capable of delivering an anchoring drug deposit to point locations in the GI tract is demonstrated. The mechanism demonstrated here is intended to complement existing ingestible capsule-based sensing and communication technologies, enabling treatment based on criteria such as detected GI biomarkers or external commands. The 3D-printed actuator has shown on command deployment in 14.1 ± 3.0 s, and a spring constant of 25.4 ± 1.4 mN mm −1 , sufficient to insert a spiny microneedle anchoring drug deposit (SMAD) into GI tissue. The complementary SMAD showed a 22-fold increase in anchoring force over traditional molded microneedles, enabling reliable removal from the actuator and robust prolonged tissue attachment. The SMAD also showed comparable drug release characteristics (R 2 = 0.9773) to penetrating molded microneedles in agarose phantom tissue with a drug spread radius of 25 mm in 168 h. The demonstrated system has the potential to enable on command delivery and anchoring of drug-loaded deposits to the GI mucosa for sustained treatment of GI inflammation while mitigating side effects and enabling new options for treatment.

Targeted Drug Delivery In article number 2201365, Reza Ghodssi and co‐workers present a 3D‐printed actuator for capsule‐based localized delivery of anchoring drug deposits to the GI tract. A thin‐film heating element enables rapid actuation and is readily compatible with currently existing ingestible sensors and electronics to target GI lesions. Firm drug anchoring is achieved via biomimetic barbed microneedles to enable reliable prolonged drug release at target locations in the GI tract.

Ingestible capsules have the potential to become an attractive alternative to traditional means of treating and detecting gastrointestinal (GI) disease. As device complexity increases, so too does the demand for more effective capsule packaging technologies to elegantly target specific GI locations. While pH-responsive coatings have been traditionally used for the passive targeting of specific GI regions, their application is limited due to the geometric restrictions imposed by standard coating methods. Dip, pan, and spray coating methods only enable the protection of microscale unsupported openings against the harsh GI environment. However, some emerging technologies have millimeter-scale components for performing functions such as sensing and drug delivery. To this end, we present the freestanding region-responsive bilayer (FRRB), a packaging technology for ingestible capsules that can be readily applied for various functional ingestible capsule components. The bilayer is composed of rigid polyethylene glycol (PEG) under a flexible pH-responsive Eudragit® FL 30 D 55, which protects the contents of the capsule until it arrives in the targeted intestinal environment. The FRRB can be fabricated in a multitude of shapes that facilitate various functional packaging mechanisms, some of which are demonstrated here. In this paper, we characterize and validate the use of this technology in a simulated intestinal environment, confirming that the FRRB can be tuned for small intestinal release. We also show a case example where the FRRB is used to protect and expose a thermomechanical actuator for targeted drug delivery.