Smart pills for gastrointestinal diagnostics and therapy
Graphical abstract
Introduction
Smart pills can be defined as an ingestible capsule containing electronic or mechanical elements that traverse the gastrointestinal (GI) tract for purposes ranging from diagnosis, treatment, sampling or surgery. These pills are easily swallowed by most people, thereby resulting in minimal discomfort, greater patient acceptance and can traverse the entire length of the GI tract. Diagnostically; these pills enable the use of novel sensors and imaging devices to improve our understanding of GI disease's aetiology with greater ease. From a therapeutic perspective, these devices open up the possibility of localised, targeted delivery of therapeutic agents to specific regions of the GI tract or systemic delivery of biologics through transepithelial delivery. The minimally invasive nature of these devices enable areas of the GI tract, such as the small intestine, to be sampled with relative ease compared to more invasive methods.
Though smart pills capable of gastric pH monitoring were first reported as far back as 1965 [1] and simple devices and smart pills for drug absorption studies along the GI tract were reported in 1961 and 1982, respectively [2], [3], it is arguably the introduction of the capsule endoscope (CE) in 2000 [4], [5] that has lead to the increase in the number of smart pills reported in recent years [6]. The CE enabled inspection of the small bowel, which was not easily accessible by conventional endoscopy. However, CE remains the most widely used smart pill in clinical practice despite the increased research activity in smart pills. The limitations of the CE as a diagnostic technology are increasingly understood due to its reliance on a single imaging modality, limiting clinical diagnosis to superficial changes in the appearance of the mucosal surface [6]. The detection of obscure GI bleeding in the small bowel is the primary recommended clinical use of these devices [7]. Integrating additional diagnostic and therapeutic modalities has the potential to improve the clinical usefulness of smart pill technology. This is exemplified by the increasing number of capsules reported in the literature in recent years. These capsules can act as a platform to better our understanding of gastrointestinal pathophysiology, provide new means of gastrointestinal and systemic therapeutic delivery, and collect tissue and other samples for subsequent analysis in a minimally invasive manner This review paper will provide an overview of current progress in this field by summarising key trends in smart pill technology. The majority of the smart pills discussed in this paper have made some progress towards clinical translation. The paper structure mirrors the three areas where these capsules are being developed for according to trends in the literature, which are diagnostic, therapeutic and sampling smart pills.
Section snippets
Smart pills for diagnosis
Various smart pills have been proposed over the years to improve the diagnosis of GI disease and improve the understanding of its causation. These diagnostic smart pills can be divided into those that either utilises imaging technology such as optical, autofluorescent imaging, or utilises sensors to detect physical changes in the GI environment, whether pressure, pH or chemical analytes. Most of the pills described in this section are in early development, with their clinical efficacy yet to be
Future directions of diagnostic smart pills
The increasing variety of sensors and imaging technologies integrated into smart pills could potentially open up diagnostic possibilities and overcome the limitations associated with CE. However, many of these technologies are immature and require further development and more extensive clinical trials to ascertain their clinical efficacy. Further development of smart pills with the capability to sense clinically established biomarkers of disease, coupled with improvements in accurately
Smart pills for therapy
Smart pills have been used to administer or support various therapies, such as the targeted delivery of small molecules, transepithelial delivery of biologics, provision of non-pharmaceutical therapies and monitoring of adherence to the therapeutic regimen. The design of these smart pills varies depending on the specific application.
Future directions for therapeutic smart pills
Whether the smart pill is being used to deliver a pharmacological or non-pharmacological treatment, there are some commonalities in the technical challenges that must be overcome to expedite translation, such as anchoring and localisation.
Anchoring is the ability of the smart pill to remain fixed in position along the GI tract while administering the treatment. The anchoring method should be able to withstand peristaltic and other forces acting on objects within the GI tract. The ability to
Smart pills for biopsy and sampling
Since their advent, smart pills have been proposed for a variety of clinical applications. One application that has received much interest is pills that can be used to conduct tissue biopsies or to sample the GI environment due to the promised benefits of reduced invasiveness and little or no patient recovery time. The surgical acquisition of tissue via endoscopic biopsy necessitates several processes to be conducted before surgery, such as fasting and bowel preparation through the ingestion of
Future directions of smart pills
This review shows that, despite the clinical potential of these devices, smart pills are still in their infancy. Despite the flurry of research activity in smart pills, many are yet to undergo the extensive in vivo testing necessary to demonstrate these technologies' diagnostic or therapeutic efficacy. The vision of autonomous smart pills capable of diagnosis with minimal clinical involvement and simultaneously applying treatment is some way off. The increased complexity of such devices may
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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