Autonomous Drug Release Systems with Disease Symptom‐Associated Triggers

Xiong, Ya; Qi, Lin; Niu, Ye; Lin, Yingbin; Zhao, Yunhui

doi:10.1002/aisy.201900124

Cited by 19 publications

(6 citation statements)

References 176 publications

(274 reference statements)

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“…[40] The porous membrane of the robotic pill was coated with a polymeric enteric-alike coating, (poly(meth)acrylate), which dissolves under physiological environmental pH conditions found in certain locations in the GI tract, thus enabling the enrichment module to open in the GI tract rather than in the stomach. [41][42][43][44] A table of pH values at various locations at the stomach and GI tract is presented in Table S1, Supporting Information. [45] The coated porous membrane was used to mimic the enteric coating of the GI tract.…”

Section: Resultsmentioning

confidence: 99%

Robotic Pill for Biomarker and Fluid Sampling in the Gastrointestinal Tract

Soto

Purcell

Özen

et al. 2022

Advanced Intelligent Systems

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Health relevant information is coded in circulating signatures or biomarkers, such as the secretome, extracellular vesicles, nucleic acids, bacteria, and other markers. [1][2][3] The collection and analysis of such signatures can serve as an early sign of disease initiation and its progression through repeated sampling. [4][5][6][7][8][9][10] Nevertheless, it remains a challenge to isolate or sample biomarkers from regions of the body with limited accessibility, such as the gastrointestinal (GI) tract, which is more than 9 meters in total length. [11,12] To gain access to these challenging locations, invasive medical procedures, such as surgery, biopsies, and colonoscopies, are required to extract information, limiting the repeatability of such measurements. [13][14][15] These techniques involve trained practitioners, expensive instruments, and specialized facilities, making them hard to expand to a large population. In contrast, minimally invasive approaches can also be used for sampling biomarkers. [16] For instance, liquid biopsy is a standard approach to obtain a snapshot of the signature pool from biofluids (blood, urine, or stool samples). [17,18] Although useful, liquid biopsy frequently provides indirect data that is averaged across the sample and not specific to a particular region of the body.Smart pills have been deployed as a method to investigate cavities inside the body. [19][20][21][22][23][24] For instance, the PillCam, an ingestible capsule with an embed camera, is commonly used to search for polyps in the GI. [25][26][27][28][29][30][31][32][33] More recently, smart pills have been applied to capture and sense biomarkers through lab-on-a-chip systems, [26][27][28] osmotic gradients, [29] and passive absorption in refs. [30][31][32] methods. The ability to isolate biomarkers within localized environments

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Section: Resultsmentioning

confidence: 99%

Robotic Pill for Biomarker and Fluid Sampling in the Gastrointestinal Tract

Soto

Purcell

Özen

et al. 2022

Advanced Intelligent Systems

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“…The porous membrane of the robotic pill was coated with polymeric enteric-alike coating, (poly(meth)acrylate), which dissolves under physiological environmental pH conditions found in certain locations in the GI tract, thus enabling the enrichment module to open in the GI tract rather than in the stomach. (Xiong et al, 2020;Li et al, 2016;Soto et al, 2021) A table of pH values at various locations at the stomach and GI tract is presented in Table 1. (Evans et al, 1988) Gastrointestinal Region pH Stomach 1.0-2.5 Proximal small intestine 6.6 Terminal ileum 7.5 Caecum 6.4 Colon 7…”

Section: Results and Disscussionmentioning

confidence: 99%

Robotic Pill for Biomarker and Fluid Sampling in the Gastrointestinal Tract

Soto

Purcell

Özen

et al. 2022

Preprint

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Developing on-site biomarker enrichment platforms could help to improve the diagnosis of gastrointestinal (GI) tract diseases at early stages. Medical procedures, such as colonoscopies and imaging techniques, are used to diagnose disease, but are not easily accessible for repeat measurements. In the other hand, liquid biopsies, e.g., blood, urine, or fecal samples, have become important sampling strategies to identify health concerns. Herein, a robotic pill is designed for collecting relevant biomarkers from the GI over prolonged sampling periods. The robotic pill comprises a magnetic core for locomotion, a delayed gate mechanism that controls sampling location based on changes in its environment, and an enrichment module that traps biomarkers in an absorbent matrix while enabling biofluid to pass through the chamber. The robotic pill was assessed to sample microparticles, proteins, and bacteria from solution. Moreover, the robotic pill was capable of directed locomotion in complex environments and docking in a targeted region against fluid flow. Utilization of an untethered robotic sampling system could provide a tool to investigate aspects of disease initiation and progression for early diagnosis and therapy monitoring.

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“…In the last few decades, smart materials have gotten a lot of attention due to their application in the biomedical field. , In particular, on-demand (signal-triggered) release was extensively studied for drug delivery purposes. , Among the triggering factors, one can mention biomolecular signals, magnetic field, mechanical force, temperature, electromagnetic (such as visible light, infrared, and radio waves) radiation, ultrasound, electrical field, and even more sophisticated signals, like breath . One of the most usable triggers for drug delivery is pH , due to its endogenous nature, which is often associated with a certain disease.…”

Section: Introductionmentioning

confidence: 99%

Time-Separated Pulse Release–Activation of an Enzyme from Alginate–Polyethylenimine Hydrogels Using Electrochemically Generated Local pH Changes

Sterin,

Tverdokhlebova,

Katz

et al. 2024

ACS Appl. Mater. Interfaces

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β-Glucosidase (EC 3.2.1.21) from sweet almond was encapsulated into pHresponsive alginate−polyethylenimine (alginate−PEI) hydrogel. Then, electrochemically controlled cyclic local pH changes resulting from ascorbate oxidation (acidification) and oxygen reduction (basification) were used for the pulsatile release of the enzyme from the composite hydrogel. Activation of the enzyme was controlled by the very same pH changes used for β-glucosidase release, separating these two processes in time. Importantly, the activity of the enzyme, which had not been released yet, was inhibited due to the buffering effect of PEI present in the gel. Thus, only a portion of the released enzyme was activated. Both enzymatic activity and release were monitored by confocal fluorescence microscopy and regular fluorescent spectroscopy. Namely, commercially available very little or nonfluorescent substrate 4-methylumbelliferyl-β-Dglucopyranoside was hydrolyzed by β-glucosidase to produce a highly fluorescent product 4-methylumbelliferone during the activation phase. At the same time, labeling of the enzyme with rhodamine B isothiocyanate was used for release observation. The proposed work represents an interesting smart release−activation system with potential applications in biomedical field.

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Autonomous Drug Release Systems with Disease Symptom‐Associated Triggers

Cited by 19 publications

References 176 publications

Robotic Pill for Biomarker and Fluid Sampling in the Gastrointestinal Tract

Robotic Pill for Biomarker and Fluid Sampling in the Gastrointestinal Tract

Robotic Pill for Biomarker and Fluid Sampling in the Gastrointestinal Tract

Time-Separated Pulse Release–Activation of an Enzyme from Alginate–Polyethylenimine Hydrogels Using Electrochemically Generated Local pH Changes

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