Thermomechanical Soft Actuator for Targeted Delivery of Anchoring Drug Deposits to the GI Tract

Abstract

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.

Sustainable Robots 4D Printing

“…[228] Another widely used sustainable technique for the fabrication of BSSA is VPP. TPETA, [83] GelMA, [84,85] AAm, [117] PEGDA, [88][89][90][91]107,113,117,130,140,147] PCLDMA, [87,103] photocurable PLA, [110] PCLDA, [86,129] gelatin, [99] photocurable chitosan-based polymer, [34] PETA, [107] photocurable alginate-based polymer, [100] PEGMA, [101] PGMEA, [108] PEGgel, [92] and PEGDMA [149] are among biodegradable materials used to make appropriate photocurable polymer for VPP technique. Biocompatibility and biodegradability can be tailored by using different base monomers, and the modulus of elasticity and strength of the final product can be modified by altering the degree of crosslinking.…”

“…This includes the development of a more stable multilayer structure, a simpler design for the multi-molecular network, and the ability to achieve more flexible reversible deformation, among other areas of improvement. [59] Regarding their applicability, biodegradable 3D/4D printed soft actuators are utilized in many fields, such as agriculture, [60] biomedicine, micro positioning, [67,79,[94][95][96][97] smart surgical instruments, [64,[98][99][100][101] soft rehabilitation devices, [98,102,103] drug delivery microswimmers, [64,67,68,70,72,73,77,84,85,88,94,34,[104][105][106][107][108] sustainable electronics devices, [109][110][111] soft smart fabrics, [64] muscle tissue membranes, [65,76,89,94,96,112,113] in-vivo robotics, [67,74,…”

“…[238] Unfortunately, because of their restricted range of mechanical and chemical characteristics, these polymers are only suitable for particular kinds of tissue replacement scaffolds. TPETA, [83] GelMA, [84,85] Acrylamide (AAm), [117] PEGDA, [88][89][90][91]107,113,117,130,140,147] photocrosslinkable polycaprolactone dimethyl acrylate (PCLDMA), [87,103] photocurable PLA, [110] photocurable polycaprolactone diacrylate (PCLDA), [86,129] gelatin, [99] photocurable chitosan-based polymer, [34] pentaerythritol tetraacrylate (PETA), [107] photocurable alginate-based polymer, [100] poly(ethylene glycol) methyl ether methacrylate (PEGMA), [101] propylene glycol methyl ether acetate (PGMEA), [108] PEGgel, [92] and polyethylene glycol dimethacrylate (PEGDMA) [149] are among biodegradable materials used to make appropriate photocurable polymer for VPP technique. In the following sections, several facets of each VPP approach have been addressed in more detail.…”

Intestinal retentive systems – recent advances and emerging approaches

“…87 A simple yet effective solution, this mechanism was further incorporated into spiny microneedle anchoring drug deposit (SMAD) and evaluated in ex vivo test beds. 88 Another device inspired by the swellable proboscis of endoparasite Pomphorhynchus laevis was developed by Yang et al (Fig. 5b).…”

“…87 A simple yet effective solution, this mechanism was further incorporated into spiny microneedle anchoring drug deposit (SMAD) and evaluated in ex vivo test beds. 88…”