Gastrointestinal tract drug delivery using algae motors embedded in a degradable capsule

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Abstract

The use of micromotors for active drug delivery via oral administration has recently gained considerable interest. However, efficient motor-assisted delivery into the gastrointestinal (GI) tract remains challenging, owing to the short propulsion lifetime of currently used micromotor platforms. Here, we report on an efficient algae-based motor platform, which takes advantage of the fast and long-lasting swimming behavior of natural microalgae in intestinal fluid to prolong local retention within the GI tract. Fluorescent dye or cell membrane–coated nanoparticle functionalized algae motors were further embedded inside a pH-sensitive capsule to enhance delivery to the small intestines. In vitro, the algae motors displayed a constant motion behavior in simulated intestinal fluid after 12 hours of continuous operation. When orally administered in vivo into mice, the algae motors substantially improved GI distribution of the dye payload compared with traditional magnesium-based micromotors, which are limited by short propulsion lifetimes, and they also enhanced retention of a model chemotherapeutic payload in the GI tract compared with a passive nanoparticle formulation. Overall, combining the efficient motion and extended lifetime of natural algae–based motors with the protective capabilities of oral capsules results in a promising micromotor platform capable of achieving greatly improved cargo delivery in GI tissue for practical biomedical applications.

Abstract

Green algae, embedded in a capsule, has been utilized as an active motor for oral drug delivery to the gastrointestinal tract.

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Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform.

Che-Ming Hu, Li. Zhang, Santosh Aryal … (2011)

Efforts to extend nanoparticle residence time in vivo have inspired many strategies in particle surface modifications to bypass macrophage uptake and systemic clearance. Here we report a top-down biomimetic approach in particle functionalization by coating biodegradable polymeric nanoparticles with natural erythrocyte membranes, including both membrane lipids and associated membrane proteins for long-circulating cargo delivery. The structure, size and surface zeta potential, and protein contents of the erythrocyte membrane-coated nanoparticles were verified using transmission electron microscopy, dynamic light scattering, and gel electrophoresis, respectively. Mice injections with fluorophore-loaded nanoparticles revealed superior circulation half-life by the erythrocyte-mimicking nanoparticles as compared to control particles coated with the state-of-the-art synthetic stealth materials. Biodistribution study revealed significant particle retention in the blood 72 h following the particle injection. The translocation of natural cellular membranes, their associated proteins, and the corresponding functionalities to the surface of synthetic particles represents a unique approach in nanoparticle functionalization.

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Cell Membrane Coating Nanotechnology

Ronnie Fang, Ashley Kroll, Weiwei Gao … (2018)

Nanoparticle-based therapeutic, prevention, and detection modalities have the potential to greatly impact how diseases are diagnosed and managed in the clinic. With the wide range of different nanomaterials available to nanomedicine researchers, the rational design of nanocarriers on an application-specific basis has become increasingly commonplace. In this review, we provide a comprehensive overview on an emerging platform: cell membrane coating nanotechnology. As one of the most fundamental units in biology, a cell carries out a wide range of functions, including its remarkable ability to interface and interact with its surrounding environment. Instead of attempting to replicate such functions via synthetic techniques, researchers are now directly leveraging naturally derived cell membranes as a means of bestowing nanoparticles with enhanced biointerfacing capabilities. This top-down technique is facile, highly generalizable, and has the potential to greatly augment the potency and safety of existing nanocarriers. Further, the introduction of a natural membrane substrate onto the surface of a nanoparticle has enabled additional applications beyond those already associated with the field of nanomedicine. Despite the relative youth of the cell membrane coating technique, there exists an impressive body of literature on the topic, which will be covered in detail in this review. Overall, there is still significant room for development, as researchers continue to refine existing workflows while finding new and exciting applications that can take advantage of this emerging technology. Cell membrane coating is an emerging nanotechnology. By cloaking nanomaterials in a layer of natural cell membrane, which can be derived from a variety of cell types, it is possible to fabricate nanoplatforms with enhanced surface functionality. This can lead to increased nanoparticle performance in complex biological environments, which can benefit applications like drug delivery, imaging, phototherapies, immunotherapies, and detoxification.

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Micro/nanorobots for biomedicine: Delivery, surgery, sensing, and detoxification

Joseph Wang, Wei Gao, Berta Esteban-Fernández de Ávila … (2017)

Micro- and nanoscale robots that can effectively convert diverse energy sources into movement and force represent a rapidly emerging and fascinating robotics research area. Recent advances in the design, fabrication, and operation of micro/nanorobots have greatly enhanced their power, function, and versatility. The new capabilities of these tiny untethered machines indicate immense potential for a variety of biomedical applications. This article reviews recent progress and future perspectives of micro/nanorobots in biomedicine, with a special focus on their potential advantages and applications for directed drug delivery, precision surgery, medical diagnosis and detoxification. Future success of this technology, to be realized through close collaboration between robotics, medical and nanotechnology experts, should have a major impact on disease diagnosis, treatment, and prevention.