Targeted temperature sensitive magnetic liposomes for thermo-chemotherapy
ABSTRACT We describe folate receptor targeted thermosensitive magnetic liposomes, which are designed to combine features of biological and physical (magnetic) drug targeting for use in magnetic hyperthermia-triggered drug release. The optimized liposome formulation DPPC:cholesterol:DSPE-PEG(2000):DSPE-PEG(2000)-Folate at 80:20:4.5:0.5 molar ratio showed calcein release of about 70% both in PBS and in 50% FBS (fetal bovine serum) at 43 degrees C and less than 5% release at 37 degrees C following 1h incubation. Folate-targeted doxorubicin-containing magnetic liposomes of the above lipid composition (MagFolDox) showed encapsulation efficiencies of about 85% and 24% for doxorubicin and magnetic nanoparticles (mean crystallite size 10nm), respectively. This magnetic formulation displayed the desired temperature sensitivity with 52% doxorubicin release in 50% fetal bovine serum (FBS) following 1h incubation at 43 degrees C. MagFolDox, when physically targeted to tumor cells in culture by a permanent magnetic field yielded a substantial increase in cellular uptake of doxorubicin as compared to Caelyx (a commercially available liposomal doxorubicin preparation), non-magnetic folate-targeted liposomes (FolDox) and free doxorubicin in folate receptor expressing tumor cell lines (KB and HeLa cells). This resulted in a parallel increase in cytotoxicity over Caelyx and FolDox. Magnetic hyperthermia at 42.5 degrees C and 43.5 degrees C synergistically increased the cytotoxicity of MagFolDox. The results suggest that an integrated concept of biological and physical drug targeting, triggered drug release and hyperthermia based on magnetic field influence can be used advantageously for thermo-chemotherapy of cancers.
- SourceAvailable from: Caterina Merla
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- "Recently the temperatureinduced controlled release has been modified using magnetic fields as triggering agents and magnetoliposomes (MLs) as drug carriers. Such carriers are hybrid systems of traditional thermo-sensitive liposomes containing superparamagnetic iron oxide nanoparticles (MNPs) and their use as devices for magnetic-controlled delivery of drugs has been investigated  . In particular, when exposed to appropriate magnetic fields (amplitudes of kA/m and frequencies from tens to hundreds of kHz) MNPs generate heat, either from hysteresis losses or from Neíel or Brownian relaxation processes . "
ABSTRACT: High-transition temperature liposomes with embedded coated magnetite nanoparticles were prepared using the thin lipid film hydration method in order to obtain magnetoliposomes not sensitive to temperature increase (at least up to 50°C). Accordingly, drug can be released from such magnetoliposomes using a low-level electromagnetic field as triggering agent, while no delivery would be obtained with temperature increase within the physiological acceptable range. The hypothesized release mechanism involves mechanical stress of the liposome membrane due to nanoparticles oscillations and it is investigated by means of a numerical model evaluated using multiphysics simulations. The carrier content was repetitively released by switching on and off a 20kHz, 60A/m magnetic field. The results indicated high reproducibility of cycle-to-cycle release induced by the magnetic-impelled motions driving to the destabilization of the bilayer rather than the liposome phase transition or the destruction of the liposome structure. Copyright © 2015. Published by Elsevier B.V.Colloids and surfaces B: Biointerfaces 04/2015; 131. DOI:10.1016/j.colsurfb.2015.04.030 · 4.15 Impact Factor
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- "The nanoparticle encapsulation efficiency has been shown to decrease if nanoparticles agglomerate prior to or during encapsulation . For example, starch coated iron oxide nanoparticles were reported primarily to be located outside the liposomes . The influence of nanoparticles interacting strongly with the lipid membrane on the liposome permeability is not quantitatively known but several examples from the literature indicate that it is substantial. "
ABSTRACT: Superparamagnetic iron oxide nanoparticles are used in a rapidly expanding number of research and practical applications in biotechnology and biomedicine. We highlight how recent developments in iron oxide nanoparticle design and understanding of nanoparticle membrane interactions have led to applications in magnetically triggered, liposome delivery vehicles with controlled structure. Nanoscale vesicles actuated by incorporated nanoparticles allow for controlling location and timing of compound release, which enables e.g. use of more potent drugs in drug delivery as the interaction with the right target is ensured. This review emphasizes recent results on the connection between nanoparticle design, vesicle assembly and the stability and release properties of the vesicles. While focused on lipid vesicles magnetically actuated through iron oxide nanoparticles, these insights are of general interest for the design of capsule and cell delivery systems for biotechnology controlled by nanoparticles.New Biotechnology 12/2014; DOI:10.1016/j.nbt.2014.12.002 · 2.90 Impact Factor
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- "Pradhan et al. (2010) proved that triggered drug release and hyperthermia induced by magnetic field can be advantageous for thermo-chemotherapy of cancers. Their results demonstrated that folate receptor targeted thermosensitive magnetic doxorubicin-loaded liposome's (MagFolDox) cytotoxicity toward cancer cells is synergistically increased by magnetic hyperthermia at 42.5 C and 43.5 C (Pradhan et al., 2010). Figure 1 illustrates reversible thermal transitions and cellular uptake of micellar-like NPs. "
ABSTRACT: Abstract Although several anticancer drugs have been introduced as chemotherapeutic agents, the effective treatment of cancer remains a challenge. Major limitations in the application of anticancer drugs include their nonspecificity, wide biodistribution, short half-life, low concentration in tumor tissue and systemic toxicity. Drug delivery to the tumor site has become feasible in recent years, and recent advances in the development of new drug delivery systems for controlled drug release in tumor tissues with reduced side effects show great promise. In this field, the use of biodegradable polymers as drug carriers has attracted the most attention. However, drug release is still difficult to control even when a polymeric drug carrier is used. The design of pharmaceutical polymers that respond to external stimuli (known as stimuli-responsive polymers) such as temperature, pH, electric or magnetic field, enzymes, ultrasound waves, etc. appears to be a successful approach. In these systems, drug release is triggered by different stimuli. The purpose of this review is to summarize different types of polymeric drug carriers and stimuli, in addition to the combination use of stimuli in order to achieve a better controlled drug release, and it discusses their potential strengths and applications. A survey of the recent literature on various stimuli-responsive drug delivery systems is also provided and perspectives on possible future developments in controlled drug release at tumor site have been discussed.Drug Delivery 02/2014; 22(2). DOI:10.3109/10717544.2014.887157 · 2.20 Impact Factor