Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Soft Capsule Magnetic Millirobots for Region-Specific Drug Delivery in the Central Nervous System.

ABSTRACT: Small soft robotic systems are being explored for myriad applications in medicine. Specifically, magnetically actuated microrobots capable of remote manipulation hold significant potential for the targeted delivery of therapeutics and biologicals. Much of previous efforts on microrobotics have been dedicated to locomotion in aqueous environments and hard surfaces. However, our human bodies are made of dense biological tissues, requiring researchers to develop new microrobotics that can locomote atop tissue surfaces. Tumbling microrobots are a sub-category of these devices capable of walking on surfaces guided by rotating magnetic fields. Using microrobots to deliver payloads to specific regions of sensitive tissues is a primary goal of medical microrobots. Central nervous system (CNS) tissues are a prime candidate given their delicate structure and highly region-specific function. Here we demonstrate surface walking of soft alginate capsules capable of moving on top of a rat cortex and mouse spinal cord ex vivo, demonstrating multi-location small molecule delivery to up to six different locations on each type of tissue with high spatial specificity. The softness of alginate gel prevents injuries that may arise from friction with CNS tissues during millirobot locomotion. Development of this technology may be useful in clinical and preclinical applications such as drug delivery, neural stimulation, and diagnostic imaging.

SUBMITTER: Mair LO

PROVIDER: S-EPMC8340882 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Pathogen-inspired drug delivery to the central nervous system.

Project description:For as long as the human blood-brain barrier (BBB) has been evolving to exclude bloodborne agents from the central nervous system (CNS), pathogens have adopted a multitude of strategies to bypass it. Some pathogens, notably viruses and certain bacteria, enter the CNS in whole form, achieving direct physical passage through endothelial or neuronal cells to infect the brain. Other pathogens, including bacteria and multicellular eukaryotic organisms, secrete toxins that preferentially interact with specific cell types to exert a broad range of biological effects on peripheral and central neurons. In this review, we will discuss the directed mechanisms that viruses, bacteria, and the toxins secreted by higher order organisms use to enter the CNS. Our goal is to identify ligand-mediated strategies that could be used to improve the brain-specific delivery of engineered nanocarriers, including polymers, lipids, biologically sourced materials, and imaging agents.

| S-EPMC4292043 | biostudies-literature

Versatile magnetic hydrogel soft capsule microrobots for targeted delivery.

Project description:Maintaining the completeness of cargo and achieving on-demand cargo release during long navigations in complex environments of the internal human body is crucial. Herein, we report a novel design of magnetic hydrogel soft capsule microrobots, which can be physically disintegrated to release microrobot swarms and diverse cargoes with almost no loss. CaCl2 solution and magnetic powders are utilized to produce suspension droplets, which are put into sodium alginate solution to generate magnetic hydrogel membranes for enclosing microrobot swarms and cargos. Low-density rotating magnetic fields drive the microrobots. Strong gradient magnetic fields break the mechanical structure of the hydrogel shell to implement on-demand release. Under the guidance of ultrasound imaging, the microrobot is remotely controlled in acidic or alkaline environments, similar to those in the human digestion system. The proposed capsule microrobots provide a promising solution for targeted cargo delivery in the internal human body.

| S-EPMC10192936 | biostudies-literature

A cell-based drug delivery platform for treating central nervous system inflammation.

Project description:Mesenchymal stem cells (MSCs) are promising candidates for the development of cell-based drug delivery systems for autoimmune inflammatory diseases, such as multiple sclerosis (MS). Here, we investigated the effect of Ro-31-8425, an ATP-competitive kinase inhibitor, on the therapeutic properties of MSCs. Upon a simple pretreatment procedure, MSCs spontaneously took up and then gradually released significant amounts of Ro-31-8425. Ro-31-8425 (free or released by MSCs) suppressed the proliferation of CD4+ T cells in vitro following polyclonal and antigen-specific stimulation. Systemic administration of Ro-31-8425-loaded MSCs ameliorated the clinical course of experimental autoimmune encephalomyelitis (EAE), a murine model of MS, displaying a stronger suppressive effect on EAE than control MSCs or free Ro-31-8425. Ro-31-8425-MSC administration resulted in sustained levels of Ro-31-8425 in the serum of EAE mice, modulating immune cell trafficking and the autoimmune response during EAE. Collectively, these results identify MSC-based drug delivery as a potential therapeutic strategy for the treatment of autoimmune diseases. KEY MESSAGES: MSCs can spontaneously take up the ATP-competitive kinase inhibitor Ro-31-8425. Ro-31-8425-loaded MSCs gradually release Ro-31-8425 and exhibit sustained suppression of T cells. Ro-31-8425-loaded MSCs have more sustained serum levels of Ro-31-8425 than free Ro-31-8425. Ro-31-8425-loaded MSCs are more effective than MSCs and free Ro-31-8425 for EAE therapy.

| S-EPMC8292974 | biostudies-literature

Learning of Sub-optimal Gait Controllers for Magnetic Walking Soft Millirobots.

Project description:Untethered small-scale soft robots have promising applications in minimally invasive surgery, targeted drug delivery, and bioengineering applications as they can access confined spaces in the human body. However, due to highly nonlinear soft continuum deformation kinematics, inherent stochastic variability during fabrication at the small scale, and lack of accurate models, the conventional control methods cannot be easily applied. Adaptivity of robot control is additionally crucial for medical operations, as operation environments show large variability, and robot materials may degrade or change over time, which would have deteriorating effects on the robot motion and task performance. Therefore, we propose using a probabilistic learning approach for millimeter-scale magnetic walking soft robots using Bayesian optimization (BO) and Gaussian processes (GPs). Our approach provides a data-efficient learning scheme to find controller parameters while optimizing the stride length performance of the walking soft millirobot robot within a small number of physical experiments. We demonstrate adaptation to fabrication variabilities in three different robots and to walking surfaces with different roughness. We also show an improvement in the learning performance by transferring the learning results of one robot to the others as prior information.

| S-EPMC7610446 | biostudies-literature

Interventional MRI-guided catheter placement and real time drug delivery to the central nervous system.

Project description:Local delivery of therapeutic agents into the brain has many advantages; however, the inability to predict, visualize and confirm the infusion into the intended target has been a major hurdle in its clinical development. Here, we describe the current workflow and application of the interventional MRI (iMRI) system for catheter placement and real time visualization of infusion. We have applied real time convection-enhanced delivery (CED) of therapeutic agents with iMRI across a number of different clinical trials settings in neuro-oncology and movement disorders. Ongoing developments and accumulating experience with the technique and technology of drug formulations, CED platforms, and iMRI systems will continue to make local therapeutic delivery into the brain more accurate, efficient, effective and safer.

| S-EPMC5553275 | biostudies-literature

Task space adaptation via the learning of gait controllers of magnetic soft millirobots.

Project description:Untethered small-scale soft robots have promising applications in minimally invasive surgery, targeted drug delivery, and bioengineering applications as they can directly and non-invasively access confined and hard-to-reach spaces in the human body. For such potential biomedical applications, the adaptivity of the robot control is essential to ensure the continuity of the operations, as task environment conditions show dynamic variations that can alter the robot's motion and task performance. The applicability of the conventional modeling and control methods is further limited for soft robots at the small-scale owing to their kinematics with virtually infinite degrees of freedom, inherent stochastic variability during fabrication, and changing dynamics during real-world interactions. To address the controller adaptation challenge to dynamically changing task environments, we propose using a probabilistic learning approach for a millimeter-scale magnetic walking soft robot using Bayesian optimization (BO) and Gaussian processes (GPs). Our approach provides a data-efficient learning scheme by finding the gait controller parameters while optimizing the stride length of the walking soft millirobot using a small number of physical experiments. To demonstrate the controller adaptation, we test the walking gait of the robot in task environments with different surface adhesion and roughness, and medium viscosity, which aims to represent the possible conditions for future robotic tasks inside the human body. We further utilize the transfer of the learned GP parameters among different task spaces and robots and compare their efficacy on the improvement of data-efficient controller learning.

| S-EPMC7612667 | biostudies-literature

Establishment of an Olfactory Region-specific Intranasal Delivery Technique in Mice to Target the Central Nervous System.

Project description:We have recently developed a region-specific catheter-based intranasal application method in mice by using CT scan-based 3D cast models of the murine nose (DOI: 10.2376/0005-9366-17,102). This technique is able to specifically deliver drugs to the olfactory region or to the respiratory region only. Thereby, intranasally administered drugs could be delivered either via neuronal connections to the central nervous system or via the well-perfused rostral parts of the nasal mucosa to the systemic circulation. In the present study, we transferred successfully this novel delivery technique to C57Bl/6 mice and determined parameters such as insertions depth of the catheter and maximum delivery volume in dependence to the weight of the mouse. Breathing was simulated to verify that the volume remains at the targeted area. A step-by-step procedure including a video is presented to adopt this technique for standardized and reproducible intranasal central nervous system (CNS) delivery studies (DOI : 10.3390/ pharmaceutics13111904).

| S-EPMC8785418 | biostudies-literature

The soft mechanical signature of glial scars in the central nervous system.

Project description:Injury to the central nervous system (CNS) alters the molecular and cellular composition of neural tissue and leads to glial scarring, which inhibits the regrowth of damaged axons. Mammalian glial scars supposedly form a chemical and mechanical barrier to neuronal regeneration. While tremendous effort has been devoted to identifying molecular characteristics of the scar, very little is known about its mechanical properties. Here we characterize spatiotemporal changes of the elastic stiffness of the injured rat neocortex and spinal cord at 1.5 and three weeks post-injury using atomic force microscopy. In contrast to scars in other mammalian tissues, CNS tissue significantly softens after injury. Expression levels of glial intermediate filaments (GFAP, vimentin) and extracellular matrix components (laminin, collagen IV) correlate with tissue softening. As tissue stiffness is a regulator of neuronal growth, our results may help to understand why mammalian neurons do not regenerate after injury.

| S-EPMC5364386 | biostudies-literature

Occurrence of Morpholine in Central Nervous System Drug Discovery.

Project description:Developing drugs for the central nervous system (CNS) requires fine chemical modifications, as a strict balance between size and lipophilicity is necessary to improve the permeability through the blood-brain barrier (BBB). In this context, morpholine and its analogues represent valuable heterocycles, due to their conformational and physicochemical properties. In fact, the presence of a weak basic nitrogen atom and of an oxygen atom at the opposite position provides a peculiar pKa value and a flexible conformation to the ring, thus allowing it to take part in several lipophilic-hydrophilic interactions, and to improve blood solubility and brain permeability of the overall structure. In CNS-active compounds, morpholines are used (1) to enhance the potency through molecular interactions, (2) to act as a scaffold directing the appendages in the correct position, and (3) to modulate pharmacokinetic/pharmacodynamic (PK/PD) properties. In this perspective, selected morpholine-containing CNS drug candidates are discussed to reveal the active pharmacophores accountable for the (1) modulation of receptors involved in mood disorders and pain, (2) bioactivity toward enzymes and receptors responsible for neurodegenerative diseases, and (3) inhibition of enzymes involved in the pathology of CNS tumors. The medicinal chemistry/pharmacological activity of morpholine derivatives is discussed, in the effort to highlight the importance of morpholine ring interactions in the active site of different targets, particularly reporting binding features retrieved from PDB data, when available.

| S-EPMC7877733 | biostudies-literature

Dendrimer advances for the central nervous system delivery of therapeutics.

Project description:The effectiveness of noninvasive treatment for central nervous system (CNS) diseases is generally limited by the poor access of therapeutic agents into the CNS. Most CNS drugs cannot permeate into the brain parenchyma because of the blood-brain barrier (BBB), and overcoming this has become one of the most significant challenges in the development of CNS therapeutics. Rapid advances in nanotechnology have provided promising solutions to this challenge. This review discusses the latest applications of dendrimers in the treatment of CNS diseases with an emphasis on brain tumors. Dendrimer-mediated drug delivery, imaging, and diagnosis are also reviewed. The toxicity, biodistribution, and transport mechanisms in dendrimer-mediated delivery of CNS therapeutic agents bypassing or crossing the BBB are also discussed. Future directions and major challenges of dendrimer-mediated delivery of CNS therapeutic agents are included.

| S-EPMC3894720 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data