Targeted temperature sensitive magnetic liposomes for thermo-chemotherapy

School of Biosciences and Bioengineering, IIT Bombay, Mumbai, India.
Journal of Controlled Release (Impact Factor: 7.71). 10/2009; 142(1):108-21. DOI: 10.1016/j.jconrel.2009.10.002
Source: PubMed


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.

25 Reads
  • Source
    • "c [77] MCIO/polymer embedded colloidal assemblies MnFe 2 O 4 /LA; Fe 3 O 4 /OA dispersed in toluene/tetrahydro furane Thermal decomposition/colloid destabilization by acetonitrile 70e134 a 43 e 2.3 Â 10À16 d [53] MCIO/CA obtained by fractionation e High temperature hydrolysis polyol approach 19.7e28.8 a 65.4e81.8 c [76] MCIO e Microwave irradiation 100 a 38.3 c [108] MCIO/polymer vesicle (Pluronic) IONP/OA dispersed in tetrahydro furane (ferrofluid) IONP embedded in polymer vesicle by microfluidic mixing ~160 a 4.1e17.4% f [99] MCIO/liposomes g-Fe 3 O 4 /citrate in water (ferrofluid) Encapsulation of IONP into the liposomes 200 a 24e33% g [51] MCIO/liposomes-PEG Fe 3 O 4 in water (suspension) Encapsulation of IONP into liposomes coated with PEG 90e110 (AFM) e [97] MCIO/liposomes-PEG/PEG-Folic acid/Doxorubicin Fe 3 O 4 in water (commercial ferrofluid) Encapsulation of IONP and doxorubicin into the liposomes coated with PEG and PEG þ Folic acid 156þÀ11 b 361þÀ20 b e [109] Size: a TEM; b DLS. Magnetic: c M s -saturation magnetization (emu/g); d m e magnetic moment (A m 2 ); e u-magnetophoretic velocity (mm/s). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent developments in nanotechnology and application of magnetic nanoparticles, in particular in magnetic iron oxide nanosystems, offer exciting possibilities for nanomedicine. Facile and precise synthesis procedures, high magnetic response, tunable morphologies and multiple bio-functionalities of single- and multi-core magnetic particles designed for nanomedicine applications are thoroughly appraised. This review focuses on the structural and magnetic characterization of the cores, the synthesis of single- and multicore iron oxide NPs, especially the design of the latter, as well as their protection, stabilization and functionalization by desired coating in order to protect against the corrosion of core, to prevent non-specific protein adsorption and particle aggregation in biological media, and to provide binding sites for targeting and therapeutic agents. Copyright © 2015. Published by Elsevier Inc.
    Biochemical and Biophysical Research Communications 08/2015; DOI:10.1016/j.bbrc.2015.08.030 · 2.30 Impact Factor
  • Source
    • "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 [8] [9]. 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 [10]. "
    [Show abstract] [Hide abstract]
    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
  • Source
    • "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 [34]. 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. "
    [Show abstract] [Hide abstract]
    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; 32(6). DOI:10.1016/j.nbt.2014.12.002 · 2.90 Impact Factor
Show more