Combined Magnetoliposome Formation and Drug Loading in One Step for Efficient Alternating Current-Magnetic Field Remote-Controlled Drug Release

Abstract

We have developed a reproducible and facile one step strategy for the synthesis of doxorubicin loaded magnetoliposomes by using a thin-layer evaporation method. Liposomes of around 200 nm were made of 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and iron oxide nanoparticles (NP) with negative, positive and hydrophobic surfaces that were incorporated outside, inside or between the lipid bilayers, respectively. To characterize how NP are incorporated in liposomes, advanced cryoTEM and atomic force microscope (AFM) techniques have been used. It was observed that only when the NP are attached outside the liposomes, the membrane integrity is preserved (lipid melt transition shifts to 38.7 ºC with high enthalpy 34.8 J/g) avoiding the leakage of encapsulated drug while having good colloidal properties and the best heating efficiency under an alternating magnetic field (AMF). These magnetoliposomes were tested with two cancer cell lines, MDA-MB-231 and HeLa cells. First, 100 % of cellular uptake was achieved with a high cell survival (above 80 %), which is preserved (83 %) for doxorubicin loaded magnetoliposomes. Then, we demonstrate that doxorubicin release can be triggered by remote control, using a noninvasive external AMF for 1 hour, leading to a cell survival reduction of 20 %. Magnetic field conditions of 202 kHz and 30 mT seem to be enough to produce an effective heating avoiding drug degradation. In conclusion, these drug loaded magnetoliposomes prepared in one step could be used for drug release on demand at a specific time and place efficiently using an external AMF reducing or even eliminating side effects.

A Novel Hybrid Nanosystem Integrating Cytotoxic and Magnetic Properties as a Tool to Potentiate Melanoma Therapy

“…The present study focused on melanoma treatment through a novel hybrid lipid-based nanosystem. To this end, liposomes with magnetic properties were prepared by passively encapsulating IONPs within the aqueous interior compartment, a method that has been employed by other research groups [39][40][41][42][43].…”

Recent progress of magnetic nanoparticles in biomedical applications: A review

“…[ 130 ] Furthermore, magnetic particles can be utilized as on demand and controlled therapeutic agent release platform into desired sites. [ 131 ] External stimuli such as alternating magnetic field can be used to release attached therapeutic molecules into targeted localized region. [ 130 ] In this section, different types of nanocarriers incorporated with magnetic particles to increase the overall efficacy of drug/gene delivery will be discussed.…”

Magnetic-field-triggered Remote Drug Release and Analysis of Mechanism

“…They believed that the temperature change induced by the magnetic thermal effect in an AMF of 100 kHz caused the shrinkage of the polymer mesh to promote the rapid release of encapsulated drug molecules and proteins. Fortes Brollo et al (5) used AMFs of 92, 202, and 282 kHz to remotely trigger the release of the anticancer drug Dox from magnetic liposomes, where MNPs were on the outer layer, in the lumen, and between the lipid bilayers, respectively. They believed that the permeability change of the lipid membrane induced by magnetic heat led to the release of the encapsulated drug regardless of the structure of the magnetic drug carrier.…”

“…(2,3) Controlled release can be achieved by the direct control of the drug release process, with the release triggered using smart materials, by changes in the surrounding environment, or by moving or controlling the implanted drug carrier using a noncontact mode to achieve noninvasive, safe, and efficient treatment. (4,5) Among various remote triggering methods, a magnetic trigger has great potential in the development of future targeted and smart drug delivery systems owing to its excellent characteristics such as nontoxicity, high efficiency, noncontact nature, simple equipment, flexible operation, and low side effects. (6) Since the concept of magnetic hyperthermia based on magnetic nanoparticles (MNPs) for cancer treatment was first proposed, research on magnetic drug carriers and magnetically triggered drug release has been widely carried out.…”