Article

Targeted temperature sensitive magnetic liposomes for thermo-chemotherapy

School of Biosciences and Bioengineering, IIT Bombay, Mumbai, India.
Journal of Controlled Release (Impact Factor: 7.26). 10/2009; 142(1):108-21. DOI: 10.1016/j.jconrel.2009.10.002
Source: PubMed

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.

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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 [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]. "
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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 [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. "
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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. "
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