Pulsed Magnetic Field Induced Fast Drug Release from Magneto Liposomes via Ultrasound Generation (original) (raw)
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Journal of Medical Imaging and Health Informatics, 2013
Pulsed Low Intensity Non-Focused Ultrasound (LINFU) was used to trigger the release from liposomes of the clinically approved Magnetic Resonance Imaging (MRI) agent Gadoteridol. The extent of the release was monitored by relaxometric measurements upon changing both ultrasound stimulus (power, application times and mode, duty cycle values) and physico-chemical variables of the theranostic agent (liposomes size, shape, chemical composition, and concentration of the encapsulated agent). The release was not heat-mediated, but promoted by mechanical interactions between the acoustic radiation waves and the soft nanovesicles. The application of pulsed LINFU led to a controlled release detectable by both Nuclear Magnetic Resonance (NMR) relaxometry and MRI. Such promising observations were followed by an in vivo proof-of-concept study on a syngeneic B16 melanoma mouse model. The obtained results demonstrated the great potential of LINFU for designing MRI-guided protocols aimed at visualizing the release of drugs from liposomal carriers. This study could bring to the development of a new therapeutic for personalized medicine.
Can Pulsed Electromagnetic Fields Trigger On-Demand Drug Release from High-Tm Magnetoliposomes?
Nanomaterials (Basel, Switzerland), 2018
Recently, magnetic nanoparticles (MNPs) have been used to trigger drug release from magnetoliposomes through a magneto-nanomechanical approach, where the mechanical actuation of the MNPs is used to enhance the membrane permeability. This result can be effectively achieved with low intensity non-thermal alternating magnetic field (AMF), which, however, found rare clinic application. Therefore, a different modality of generating non-thermal magnetic fields has now been investigated. Specifically, the ability of the intermittent signals generated by non-thermal pulsed electromagnetic fields (PEMFS) were used to verify if, once applied to high-transition temperature magnetoliposomes (high-Tm MLs), they could be able to efficiently trigger the release of a hydrophilic model drug. To this end, hydrophilic MNPs were combined with hydrogenated soybean phosphatidylcholine and cholesterol to design high-Tm MLs. The release of a dye was evaluated under the effect of PEMFs for different times. ...
Moscow University Chemistry Bulletin, 2020
Magnetic anionic liposomes (MALip) conjugated with magnetite magnetic nanoparticles (MNPs) are developed for the controlled release of a protease inhibitor (BBI) under exposure to a low-frequency nonheating magnetic field (LF AMF). It is shown that an increase of up to 35% of the protein release rate occurred when the MALip are exposed to the LF AMF (frequency 110 Hz, intensity 75-150 kA/m) for 5-15 min. The research provides prospects for the development of remotely controlled protein release from liposomes.
Journal of Colloid and Interface Science, 2019
Hypothesis-Magnetic liposomes are shown to release the entrapped dye once modulated by low frequency AC MF. The mechanism and effectiveness of MF application should depend on lipid composition, magnetic nanoparticles (MNPs) properties, temperature and field parameters. Experiments-The study was performed using liposomes of various lipid composition and embedded hydrophobic MNPs. The liposomes structural changes were studied by the transmission electron microscopy (TEM) and attenuated total reflection Fourier transfer infrared (ATR-FTIR) spectroscopy and the leakage was monitored by the fluorescent dye release. Findings-Magnetic liposomes exposure to the AC MF resulted in the clustering of the MNPs in the membranes and disruption of the lipid packaging. Addition of cholesterol diminished the dye release from the saturated lipid-based liposomes. Replacement of the saturated lipid for unsaturated one also decreased the dye release. The dye release depended on the strength, but not the frequency of the field. Thus, the oscillating motion of MNPs in AC MF ruptures the gel phase membranes of saturated lipids. As the temperature increases the disruption also increases. In the *
Nanomedicine: Nanotechnology, Biology and Medicine, 2019
This work presents direct evidence of disordering of liposomal membranes by magnetic nanoparticles during their exposures to nonheating alternating Extremely Low Frequency Magnetic Field (ELF MF). Changes in the lipid membrane structure were demonstrated by the Attenuated total reflection Fourier Transform Infrared and fluorescence spectroscopy. Specifically, about 50% of hydrophobic chains became highly mobile under the action of ELF MF. Magnetic field-induced increase in the membrane fluidity was accompanied by an increase in membrane permeability and release of solutes entrapped in liposomes. The effect of ELF MF on the membrane fluidity was greater in case of 70 × 12 nm magnetite nanorods adsorbed on the liposomes surface compared to liposomes with~7 nm spherical MNPs embedded within lipid membranes. A physical model of this process explaining experimental data is suggested. The obtained results open new horizons for the development of systems for triggered drug release without dangerous heating and overheating of tissues.
Two types of magnetite-containing liposomes for magnetocontrolled drug release
Journal of Physics: Conference Series, 2019
The paper is dedicated to a comparative study of pharmaceutical properties of magnetite containing liposomes. We have investigated two types of liposomes: 1) magnetic shell liposomes containing magnetic nanoparticles in the coating lipid bilayer and 2) magnetic core liposomes containing the nanoparticles in the internal volume (water phase). Both types of liposomes were obtained by the thin film hydration method from phosphatidylcholine and cholesterol. Fluorescent dye 5,6-carboxyfluorescein was used as a marker substance to indicate release. The dimensional characteristics, the degree of dye release under the influence of an alternating magnetic field, the speed of spontaneous release and the stability of liposomes during storage were investigated. It has been shown that liposomes with nanoparticles in the internal space are more stable, have low rate of spontaneous release of the incorporated substance, but the rate of release under the influence of an alternating field is also lo...
MR-Guided Drug Release From Liposomes Triggered by Thermal and Mechanical Ultrasound-Induced Effects
Frontiers in Physics, 2020
One of the most challenging tasks of the cancer research is the enhancement of the amount of the chemotherapeutic agent that can reach the target site. To achieve this goal, nanovectors capable of encapsulating the drug and releasing it following a specific stimulus have been developed. In light of this, a key point is the necessity to monitor the effective drug release through a safe and highly performing imaging technology such as Magnetic Resonance Imaging (MRI). Liposomes are highly biocompatible nanovesicles that consist of bilayered phospholipid-based membrane encompassing an aqueous core. Almost 20 drug-loaded liposomes are currently approved for clinical use in USA and EU countries. If a liposomal nanomedicine is loaded with an MRI agent whose contrast is sensitive to the microenvironment and with a release kinetics similar to the co-transported drug, the system can act as an imaging reporter of drug release. This Perspective will offer a critical and brief overview of using MRI not only to verify and monitor the release process but also as a valuable tool to predict the therapeutic outcome. In particular, it will be presented representatives preclinical studies illustrating the in vivo potential of MRI-guided drug release protocols triggered by thermal and mechanical ultrasound-induced effects. Considering the therapeutic advantages of this approach, the possible benefits in reducing the side effects and the good results reported at preclinical level, there is a reasonable hope that the near future could witness the entrance in clinical routine of MRI-guided procedures supporting ultrasound-induced drug release protocols.
Nanomedicine: Nanotechnology, Biology and Medicine, 2014
The work aimed at developing a MRI-guided protocol for the visualization of the release of material entrapped in liposomes stimulated by the local application of pulsed low-intensity non-focused ultrasound (pLINFU). The task was achieved by formulating liposomes filled up with the clinically approved paramagnetic agent gadoteridol, because the release of the agent from the nanovesicles is accompanied by a significant MRI signal enhancement. The protocol was validated in vivo on mice-bearing subcutaneous syngeneic B16 melanoma and i.v. injected with the paramagnetic liposomes. Upon exposing tumor to pLINFU (3 MHz, insonation time 2 min, duty cycle 50%) few minutes after liposomes injection, a signal enhancement of ca. 35% was detected. The effective release of the agent was confirmed by the strong enhancement measured in kidneys calyx and bladder due to the rapid renal excretion of the agent released in the tumor.
Magnetic nanoparticles for "smart liposomes
European biophysics journal : EBJ, 2015
Liposomal drug delivery systems (LDDSs) are promising tools used for the treatment of diseases where highly toxic pharmacological agents are administered. Currently, destabilising LDDSs by a specific stimulus at a target site remains a major challenge. The bacterial mechanosensitive channel of large conductance (MscL) presents an excellent candidate biomolecule that could be employed as a remotely controlled pore-forming nanovalve for triggered drug release from LDDSs. In this study, we developed superparamagnetic nanoparticles for activation of the MscL nanovalves by magnetic field. Synthesised CoFe2O4 nanoparticles with the radius less than 10 nm were labelled by SH groups for attachment to MscL. Activation of MscL by magnetic field with the nanoparticles attached was examined by the patch clamp technique showing that the number of activated channels under ramp pressure increased upon application of the magnetic field. In addition, we have not observed any cytotoxicity of the nano...
MAGNETIC DRUG DELIVERY AND TARGETING: PRINCIPLES AND APPLICATIONS
2009
Background: Nanomaterials are at the leading edge of the rapidly developing field of nanotechnology. Magnetic nanoparticles for cancer therapy and diagnosis have been developed on the basis of their unique physico-chemical properties not present in other materials. Their versatility is widely exploited in such diverse techniques as cell and macromolecule separation and purification, immunoassays, targeted drug delivery, controlled material release, electromagnetic hyperthermia, gene therapy, or magnetic resonance imaging. In this review we concentrate on the physical principles of magnetic drug targeting and biomedical applications of this technique.