Endolysosomal environment-responsive photodynamic nanocarrier to enhance cytosolic drug delivery via photosensitizer-mediated membrane disruption

· We propose multi-loci and multi-site current patterning (sequential or simultaneous) for precise, rapid and repeatable steering for improved neuronal targeting.· Here we demonstrate these improvements by using a unique pixel cell for excitation synthesis as enabled by a three-layer dense magnetic coil array that is mapped to a hexagonal grid with cubic coordinates.· We validate the theory with supporting simulations, experimental results and a scalable electronics design that can address a relevant range of larger coil diameters, higher power levels and topologies.<a></a>· Precise, rapid and repeatable patterns potentially offer new modalities for noninvasive neuromodulation (suprathreshold and subthreshold) and adjacent biomagnetic applications such as tumor cell membrane disruption [1], and magnetic drug delivery [2].

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A Dense Magnetic Coil Array with Multi-locus and Multi-site Patterning

10.36227/techrxiv.16992559.v1 ◽

2021 ◽

Author(s):

Matthew Smith ◽

Daniel Sievenpiper

Keyword(s):

Drug Delivery ◽

Membrane Disruption ◽

Coil Array ◽

Tumor Cell Membrane ◽

Magnetic Coil ◽

Magnetic Drug Delivery ◽

Higher Power ◽

Cell Membrane Disruption ◽

Noninvasive Neuromodulation ◽

Relevant Range

· We propose multi-loci and multi-site current patterning (sequential or simultaneous) for precise, rapid and repeatable steering for improved neuronal targeting.· Here we demonstrate these improvements by using a unique pixel cell for excitation synthesis as enabled by a three-layer dense magnetic coil array that is mapped to a hexagonal grid with cubic coordinates.· We validate the theory with supporting simulations, experimental results and a scalable electronics design that can address a relevant range of larger coil diameters, higher power levels and topologies.<a></a>· Precise, rapid and repeatable patterns potentially offer new modalities for noninvasive neuromodulation (suprathreshold and subthreshold) and adjacent biomagnetic applications such as tumor cell membrane disruption [1], and magnetic drug delivery [2].

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The Influence of Irreversibly Electroporated Cells on Post Pulse Drug Delivery to Reversibly Electroporated Cells

10.1101/2021.06.23.446669 ◽

2021 ◽

Author(s):

Sid M Becker

Keyword(s):

Drug Delivery ◽

Cell Death ◽

Continuum Model ◽

Drug Uptake ◽

Membrane Disruption ◽

Transmembrane Transport ◽

High Porosity ◽

Transient Behaviour ◽

Dilute Suspensions ◽

Low Porosity

Electroporation can result in cell death in some proportion of a population of cells and, because the nature of the membrane disruption can vary significantly in irreversibly electroporated cells, there is uncertainty in the magnitude of and the transient behaviour of the associated permeability increases. This study numerically investigates the drug uptake by a population of cells that includes both reversibly and irreversibly electroporated cells. A theoretical continuum model is developed and simulations are conducted in conditions of low porosity (cells in tissues) and of high porosity (cells in suspension). This model estimates the permeability increases of electroporated cells using empirically based predictions of the dependence of long-lived electropore density on the local electric field magnitude. A parametric investigation investigates how the transmembrane transport characteristics of irreversibly electroporated cells (permeability and resealing rate) affect the drug uptake of the surviving cells. The results show that the magnitude and duration of the permeability increases of irreversibly electroporated cells is much more influential in low porosity tissues than in high porosity dilute suspensions. In applications of electroporation of cells in tissues, the uncertainty of irreversibly electroporated cells should be considered in regions of tissue experiencing field strengths for which the fraction of the total cells that are irreversibly electroporated exceeds about 0.1.

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Enhanced drug delivery via hyperthermal membrane disruption using targeted gold nanoparticles with PEGylated Protein-G as a cofactor

Nanomedicine Nanotechnology Biology and Medicine ◽

10.1016/j.nano.2013.04.002 ◽

2013 ◽

Vol 9 (8) ◽

pp. 1214-1222 ◽

Cited By ~ 32

Author(s):

Xinghua Sun ◽

Guandong Zhang ◽

Robert S. Keynton ◽

Martin G. O'Toole ◽

Dhruvinkumar Patel ◽

...

Keyword(s):

Drug Delivery ◽

Gold Nanoparticles ◽

Membrane Disruption ◽

Protein G ◽

Pegylated Protein

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An amphipathic lytic peptide for enhanced and selective delivery of ellipticine

Journal of Materials Chemistry B ◽

10.1039/c6tb00529b ◽

2016 ◽

Vol 4 (24) ◽

pp. 4348-4355 ◽

Cited By ~ 4

Author(s):

Sheng Lu ◽

Yong Ding ◽

Yan Wu ◽

Rong Wang ◽

Ran Pan ◽

...

Keyword(s):

Drug Delivery ◽

Bacterial Infection ◽

Membrane Disruption ◽

Lytic Peptide ◽

Selective Membrane ◽

Selective Delivery ◽

Lytic Peptides

Cationic lytic peptides (CLPs) have shown promise in treating bacterial infection and cancer via selective membrane disruption but are seldom studied for drug delivery potential.

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Techniques For The Preparation of Tissue Samples Containing Injectable Polymer Microcapsules

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100120242 ◽

1985 ◽

Vol 43 ◽

pp. 710-711

Author(s):

G.E. Visscher ◽

R. L. Robison ◽

G. J. Argentieri

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Gastrocnemius Muscle ◽

Degradation Process ◽

Delivery Systems ◽

Tissue Reaction ◽

Electron Microscopic ◽

Tissue Samples ◽

Injectable Polymer ◽

Microscopic Techniques

The use of various bioerodable polymers as drug delivery systems has gained considerable interest in recent years. Among some of the shapes used as delivery systems are films, rods and microcapsules. The work presented here will deal with the techniques we have utilized for the analysis of the tissue reaction to and actual biodegradation of injectable microcapsules. This work has utilized light microscopic (LM), transmission (TEM) and scanning (SEM) electron microscopic techniques. The design of our studies has utilized methodology that would; 1. best characterize the actual degradation process without artifacts introduced by fixation procedures and 2. allow for reproducible results.In our studies, the gastrocnemius muscle of the rat was chosen as the injection site. Prior to the injection of microcapsules the skin above the sites was shaved and tattooed for later recognition and recovery. 1.0 cc syringes were loaded with the desired quantity of microcapsules and the vehicle (0.5% hydroxypropylmethycellulose) drawn up. The syringes were agitated to suspend the microcapsules in the injection vehicle.

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Nanotheranostic agents for neurodegenerative diseases

Emerging Topics in Life Sciences ◽

10.1042/etls20190141 ◽

2020 ◽

Vol 4 (6) ◽

pp. 645-675

Author(s):

Parasuraman Padmanabhan ◽

Mathangi Palanivel ◽

Ajay Kumar ◽

Domokos Máthé ◽

George K. Radda ◽

...

Keyword(s):

Drug Delivery ◽

Neurodegenerative Diseases ◽

Cell Types ◽

Specific Cell ◽

Ageing Population ◽

Target Tissue ◽

Therapeutic Approaches ◽

Surface Receptors ◽

Theranostic Agents ◽

Preclinical Animal Models

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.

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