Magnetoliposomes Based on Shape Anisotropic Calcium/Magnesium Ferrite Nanoparticles as Nanocarriers for Doxorubicin

Abstract

Multifunctional lipid nanocarriers are a promising therapeutic approach for controlled drug release in cancer therapy. Combining the widely used liposome structure with magnetic nanoparticles in magnetoliposomes allies, the advantages of using liposomes include the possibility to magnetically guide, selectively accumulate, and magnetically control the release of drugs on target. The effectiveness of these nanosystems is intrinsically related to the individual characteristics of the two main components—lipid formulation and magnetic nanoparticles—and their physicochemical combination. Herein, shape-anisotropic calcium-substituted magnesium ferrite nanoparticles (Ca0.25Mg0.75Fe2O4) were prepared for the first time, improving the magnetic properties of spherical counterparts. The nanoparticles revealed a superparamagnetic behavior, high saturation magnetization (50.07 emu/g at 300 K), and a large heating capacity. Furthermore, a new method for the synthesis of solid magnetoliposomes (SMLs) was developed to enhance their magnetic response. The manufacturing technicalities were optimized with different lipid compositions (DPPC, DPPC/Ch, and DPPC/DSPE-PEG) originating nanosystems with optimal sizes for biomedical applications (around or below 150 nm) and low polydispersity index. The high encapsulation efficiency of doxorubicin in these magnetoliposomes was proven, as well as the ability of the drug-loaded nanosystems to interact with cell membrane models and release DOX by fusion. SMLs revealed to reduce doxorubicin interaction with human serum albumin, contributing to a prolonged bioavailability of the drug upon systemic administration. Finally, the drug release kinetic assays revealed a preferable DOX release at hyperthermia temperatures (42 °C) and acidic conditions (pH = 5.5), indicating them as promising controlled release nanocarriers by either internal (pH) and external (alternate magnetic field) stimuli in cancer therapy.

Development of pH-Sensitive Magnetoliposomes Containing Shape Anisotropic Nanoparticles for Potential Application in Combined Cancer Therapy

“…Shape anisotropic magnetic nanoparticles of magnesium ferrite with 25% replacement by calcium ions (Mg 0.75 Ca 0.25 Fe 2 O 4 ) were prepared using an adapted protocol previously described by Cardoso et al [ 23 ]. To synthesize MNPs with anisotropic shape, several surfactants can be used as shape inducing agents [ 38 ].…”

“…Solid magnetoliposomes loaded with doxorubicin were prepared following the method described in Ref [ 23 ]. For this purpose, the lipids DOPE, Ch and CHEMS were used at the molar ratio of 45:45:10, respectively.…”

“…For this purpose, the lipids DOPE, Ch and CHEMS were used at the molar ratio of 45:45:10, respectively. According to Ref [ 23 ], a thin lipid film with 2/3 of 1 mM of DOPE:Ch:CHEMS was prepared by solvent evaporation under a nitrogen flow. To this film, 3 mL of heptane was added, and this solution was ultrasonicated at 190 W for 10 min.…”

“…Hirazawa et al [ 21 ] reported that the partial replacement of Mg 2+ ions by Ca 2+ in magnesium ferrite nanoparticles (Mg 1-x Ca x Fe 2 O 4 ) favors biocompatibility, magnetization and thermal energy dissipation under an external magnetic field. The heating efficiency of nanoparticles with shape anisotropy, i.e., non-spherical, has shown clear advantages [ 22 , 23 , 24 , 25 ]. For instance, the easier magnetization along their longest axis gives them a longer blood circulation time and better magnetic and hyperthermia properties [ 26 ].…”

Microfluidic Synthesis and Purification of Magnetoliposomes for Potential Applications in the Gastrointestinal Delivery of Difficult-to-Transport Drugs

“…Liposomes with encapsulated MNPs, called magnetoliposomes (MLPs), have been extensively used as carriers in the pharmaceutical industry due to their ability to release various active molecules at a given site without the need for molecularly targeted agents [17]. This is in addition to the improvement in the biocompability, drug delivery rate for some compounds, and cellular uptake without a significant reduction in the activity of the functional compounds immobilized and delivered employing MNPs [18,19]. Moreover, these novel drug delivery vehicles might offer potential improvements in targeting, stabilization of antimicrobial agents, and gastroretention.…”