Computationally Guided Intracerebral Drug Delivery via Chronically Implanted Microdevices

Ramadi, Khalil B.; Bashyam, Ashvin; Frangieh, Chris J.; Rousseau, Erin B.; Cotler, Max J.; Langer, Robert; Graybiel, Ann M.; Cima, Michael J.

doi:10.1016/j.celrep.2020.107734

Cited by 7 publications

(3 citation statements)

References 61 publications

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“…The high flow rate induces damage to tissues at the infusion site and induces backflow along the insertion tract. At the same time, the large cannula can lead to inflammation, tissue damage, and scarring around the device [55].…”

Section: Convection-enhanced Deliverymentioning

confidence: 99%

An Overview on the Physiopathology of the Blood–Brain Barrier and the Lipid-Based Nanocarriers for Central Nervous System Delivery

Susa,

Arpicco,

Pirri

et al. 2024

Pharmaceutics

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The state of well-being and health of our body is regulated by the fine osmotic and biochemical balance established between the cells of the different tissues, organs, and systems. Specific districts of the human body are defined, kept in the correct state of functioning, and, therefore, protected from exogenous or endogenous insults of both mechanical, physical, and biological nature by the presence of different barrier systems. In addition to the placental barrier, which even acts as a linker between two different organisms, the mother and the fetus, all human body barriers, including the blood–brain barrier (BBB), blood–retinal barrier, blood–nerve barrier, blood–lymph barrier, and blood–cerebrospinal fluid barrier, operate to maintain the physiological homeostasis within tissues and organs. From a pharmaceutical point of view, the most challenging is undoubtedly the BBB, since its presence notably complicates the treatment of brain disorders. BBB action can impair the delivery of chemical drugs and biopharmaceuticals into the brain, reducing their therapeutic efficacy and/or increasing their unwanted bioaccumulation in the surrounding healthy tissues. Recent nanotechnological innovation provides advanced biomaterials and ad hoc customized engineering and functionalization methods able to assist in brain-targeted drug delivery. In this context, lipid nanocarriers, including both synthetic (liposomes, solid lipid nanoparticles, nanoemulsions, nanostructured lipid carriers, niosomes, proniosomes, and cubosomes) and cell-derived ones (extracellular vesicles and cell membrane-derived nanocarriers), are considered one of the most successful brain delivery systems due to their reasonable biocompatibility and ability to cross the BBB. This review aims to provide a complete and up-to-date point of view on the efficacy of the most varied lipid carriers, whether FDA-approved, involved in clinical trials, or used in in vitro or in vivo studies, for the treatment of inflammatory, cancerous, or infectious brain diseases.

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Section: Convection-enhanced Deliverymentioning

confidence: 99%

An Overview on the Physiopathology of the Blood–Brain Barrier and the Lipid-Based Nanocarriers for Central Nervous System Delivery

Susa,

Arpicco,

Pirri

et al. 2024

Pharmaceutics

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show abstract

“…If these approaches became feasible for clinical treatments, they would revolutionize how we treat neurological and psychiatric disorders. However, the majority of these spatially-specific neuromodulation tools rely on surgical delivery of molecules 15,16 , or device implantation [17][18][19] , which are invasive and damage the tissue, or on gene therapy, which is expensive and typically restricted to a single administration due to immune response directed to the most commonly used gene delivery vectors [20][21][22] . Finally, when neuromodulation is powered with a device, these devices can be bulky, restrict the motion of research animals, are infeasible when targeting large swathes of the brain, and in the case of clinical translation -can present social challenges.…”

Section: Introductionmentioning

confidence: 99%

Engineering Regionally-Activated Drugs for Neuroscience

Huang,

Mitrofan,

Nouraein

et al. 2023

Preprint

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The brain is comprised of multiple regions performing distinct functions. Within each of these regions, there are multiple cell types that can affect brain physiology. Finally, within each cell there are multiple signaling pathways, that, when activated or inhibited, control the cell activity, and consequently the brain function. For these reasons, methods that can control the brain with regional, cell-type, and molecular precision have been widely used in neuroscience. However, so far, achieving sustained control over a brain region with that level of specificity relied either on gene delivery or placement of invasive devices. While gene therapy holds great promise, the risks of genomic integration, vector toxicity, vector-directed immune response, high cost, and gene delivery to the brain pose significant challenges. On the other hand, invasive devices enable site-specific delivery of drugs but can also surgically damage the modulated brain region, carrying risks of infection and hemorrhage. Here, we present a new approach that can provide multi-day, noninvasive, site-specific control over specific cell types in the brain without the need to use invasive devices or gene delivery. To achieve this, we introduce a new paradigm called Regionally Activated Interstitial Drugs, or RAID, which delivers a protein-based catalytic centers, or RAID enzymes, to the brain using focused ultrasound blood-brain barrier opening. This catalytic center is designed to attach to the interstitial space in the brain where it remains for days after initial delivery. While the catalytic center is present in the brain, it can locally process an inert BBB permeable prodrug into an active drug, resulting in localized therapy. Our proof-of concept studies demonstrated that the engineered RAID enzymes can retain activity in the brain parenchyma for several days, allowing for noninvasive site-specific induction of neuronal activity that was sufficiently potent to elicit behavioral effects. Overall, the RAID paradigm enabled noninvasive, tunable, temporally-resolved, site-specific, non-genetic, neuromodulation over multiple days. The RAID paradigm is versatile and can be applied to any enzyme and prodrug pair to control various aspects of central nervous system physiology.

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“…For example, Stryker NAV3i and Tianji Orthopaedic Hand Robot have been widely used in joint replacement, spine, otolaryngology and other fields 14, 15 . In surgical scenes such as neurosurgery and orthopaedics, patient operational space and imaging space are accurate and rigid registration which are belongs to the rigid‐calibrated system (RCS) 16 …”

Section: Introductionmentioning

confidence: 99%

A robotic puncture system with optical and mechanical feedback under respiratory motion

Zhang

Bao

et al. 2022

Robotics Computer Surgery

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Puncture robot can improve the accuracy and efficiency of puncture surgery, such as thoracoabdominal and liver puncture. However, as soft tissue is deformed and shifted under respiratory motion and during the puncture process, the needle is pulled, resulting in the needle's bending and deformation, which increases the risks and sufferings of the patient, a robotic puncture system with optical and mechanical feedback is necessary. Therefore, this paper proposes a multi-information sensing 'guide-clamp' end effector for puncture surgery to accurately detect the posture and force on the puncture needle in real time. And gravity bias method with trajectory planning and the compensational controlling model are also proposed to offset the interference of self-weight and achieve zero force following. This system is evaluated by the experiments of robot controlling and human tissue simulation and the results prove the excellent robustness of the system, which meet the clinical requirement.

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Computationally Guided Intracerebral Drug Delivery via Chronically Implanted Microdevices

Cited by 7 publications

References 61 publications

An Overview on the Physiopathology of the Blood–Brain Barrier and the Lipid-Based Nanocarriers for Central Nervous System Delivery

An Overview on the Physiopathology of the Blood–Brain Barrier and the Lipid-Based Nanocarriers for Central Nervous System Delivery

Engineering Regionally-Activated Drugs for Neuroscience

A robotic puncture system with optical and mechanical feedback under respiratory motion

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