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.
Highlights
Liposomes are one of the most well-studied and well-investigated nanocarriers for drug delivery
The Ca/Mg mixed ferrite was defined through adaptation of magnesioferrite CIF file nr. 1011245, considering the distribution of cations across the tetrahedral and octahedral sites according to stoichiometry
Average hydrodynamic sizeday is slightly. These results show that the nanosystems are completely stable for days
Summary
Liposomes are one of the most well-studied and well-investigated nanocarriers for drug delivery. Liposomes have been used as a passive targeting strategy due to the gaps within the range of 100 to 780 nm between endothelial cells of tumor capillaries and the lack of lymphatic. Pharmaceutics 2021, 13, 1248 drainage—which is a phenomenon known as the Enhanced Permeability and Retention (EPR) effect [4]. The modifications that occur in the nanocarriers surface can significantly affect their circulation time [7]. PEGylated liposomes ( known as stealth liposomes) contribute to a prolonged systemic circulation by protecting the active moiety from the immune system, changing its physicochemical properties (as the hydrodynamic size) and providing hydrophilicity to hydrophobic drugs without changing their mechanism of action. It is reported that the liposomes’ ability to interact and release drugs in the target is reduced [1], and passive targeting needs to be complemented with other strategies
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