(484b) Synthesis and Hyperthermia Application of Drug Loaded Magnetic Nanostructured Lipid Carriers (MNLC)

Magnetic nanoparticles (MNPs) have been used in many biomedical applications, such as magnetic hyperthermia, magnetic resonance imaging and drug delivery systems. [1] Magnetic hyperthermia (MHP) is based on induction heating of MNPs under the application of an alternating magnetic field (AMF) and the temperature increase in body tissues leading to cellular structure change. In high temperature, such as 40-43°C cancerous cells would be damaged but healthy cells survive. Basically, MHP is focused on the destruction of tumors by heat, which is obtained from magnetic nanoparticles under AMF [2].

In literature, it is seen that MNPs are often used in conjuction with different drug delivery systems, such as micelles [1], liposomes [2], hydrogels [3], solid lipid nanoparticles (SLN) [4] and magnetic/gold nano-hybrids [5]. SLN have advantages, such as good biocompatibility and low toxicity, when compared with the emulsions and polymeric nanoparticles in drug delivery systems. However, low drug loading and leaking cause some problems in terms of drug delivery in SLN [4]. To overcome these drawbacks, second generation lipid based nanoparticles, which called as Nanostructured Lipid Carriers (NLC) are developed. NLC contain solid and liquid lipid blending, which consist less ordered crystal structure with imperfections and this structure provide high drug loading and prevent drug leaking. Also, NLC have some other advantages such as high biocompatibility, controlled drug release profiles and scale up production possibility [6].

Magnetic nanoparticles containing NLC systems are not used in the drug delivery application to our knowledge. Using NLC and magnetic nanoparticles together for hyperthermia application is a new type of drug delivery system and has a big potential in the treatment of cancer. In accordance with this purpose, MNPs embedded NLC were developed, synthesized and hyperthermia potential of these particles were investigated.

In this work, iron oxide nanoparticles (MNPs) were synthesized via a well known co-precipitation method. Magnetic nanoparticles were stabilized by using oleic acid. These MNPs show superparamagnetic behavior with high magnetization saturation value. To obtain MNPs embedded NLC, magnetic nanoparticles are added to lipid particles during the NLC synthesis. In NLC synthesis, stearic acid and oleic acid were used as solid and liquid lipids; as organic phase acetone-ethanol mixture and as an emulsifier Pluoronic F-127 were used. To determine optimum amount of embedded MNPs, different ratios were studied. Synthesized particles were characterized by Dynamic and Static Light Scattering (LS), Atomic Force Microscopy (AFM), Differential Scanning Calorimetry (DSC), Transmission Electron Microscopy (TEM), Vibrating Sample Magnetometer (VSM) and Thermo-gravimetric Analysis (TGA). The nanostructures in NLC were determined via TEM as multiple oil in fat in water (o/f/w) type with oil nano-compartments. Two different size distributions were observed from TEM images; the size of NLC without MNPs were 57±16 nm and 124±17 nm with spherical shape and the size of NLC with MNPs were 65±15 nm and 125±21 nm. To investigate the hyperthermia potential of these particles, different parameters were studied such as lipid concentration, magnitude of magnetic field and application time period. AMF were applied to the particles and temperature increase were observed. Furthermore, Specific Absorption Rate (SAR) or Specific Loss Power (SLP) were calculated, which is an another important factor for hyperthermia application. SAR is defined as, the amount of heat released by a unit weight of material per unit time during AMF [5]. Compared to other particles in literature, SAR values are relatively higher. Additionally, temperature increase of particles was studied under AMF and maximum temperature increase (Î?T_max) was obtained as 16°C after 30 minutes. Also, simulating drug encapsulated MNPs embedded NLC were used as drug delivery agent. The drug release performance of these NLC were studied with applied AMF for 5, 15 and 30 minutes at 37°C to stimulate the body temperature. Besides, drug release properties of the samples at which the AMF has not been applied were investigated as a control group. From the study it is observed that, drug release performance of NLC was increased with increasing application time period of magnetic field. This work demonstrated that, magnetic nanoparticle embedded NLC can be used in hyperthermia application successfully and also they can be thought as drug delivery systems.

References

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