Liposomes Loaded with Cisplatin and Magnetic Nanoparticles: Physicochemical Characterization, Pharmacokinetics, and In-Vitro Efficacy.

With the aim improving drug delivery, liposomes have been employed as carriers for chemotherapeutics achieving promising results; their co-encapsulation with magnetic nanoparticles is evaluated in this work. The objective of this study was to examine the physicochemical characteristics, the pharmacokinetic behaviour, and the efficacy of pegylated liposomes loaded with cisplatin and magnetic nanoparticles (magnetite) (Cis-MLs). Cis-MLs were prepared by a modified reverse-phase evaporation method. To characterize their physicochemical properties, an evaluation was made of particle size, ζ-potential, phospholipid and cholesterol concentration, phase transition temperature (Tm), the encapsulation efficiency of cisplatin and magnetite, and drug release profiles. Additionally, pharmacokinetic studies were conducted on normal Wistar rats, while apoptosis and the cytotoxic effect were assessed with HeLa cells. We present a method for simultaneously encapsulating cisplatin at the core and also embedding magnetite nanoparticles on the membrane of liposomes with a mean vesicular size of 104.4 ± 11.5 nm and a ζ-potential of -40.5 ± 0.8 mV, affording a stable formulation with a safe pharmacokinetic profile. These liposomes elicited a significant effect on cell viability and triggered apoptosis in HeLa cells.

The Therapeutic Potential of Chemo/Thermotherapy with Magnetoliposomes for Cancer Treatment.

Cancer represents a very grave and quickly growing public health problem worldwide. Despite the breakthroughs in treatment and early detection of the disease, an increase is projected in the incidence rate and mortality during the next 30 years. Thus, it is important to develop new treatment strategies and diagnostic tools. One alternative is magnetic hyperthermia, a therapeutic approach that has shown promising results, both as monotherapy and in combination with chemo- and radiotherapy. However, there are still certain limitations and questions with respect to the safety of the systemic administration of magnetic nanoparticles. To deal with these issues, magnetoliposomes were conceived as a new generation of liposomes that incorporate superparamagnetic nanoparticles and oncological pharmaceuticals within their structure. They have the advantage of targeted and selective drug delivery to the diseased organs and tissues. Some of them can avoid the immune response of the host. When exposed to a magnetic field of alternating current, magnetoliposomes produce hyperthermia, which acts synergistically with the released drug. The aim of the present review is to describe the most recent advances in the use of magnetoliposomes and point out what research remains to be done for their application to chemo-thermal therapy in cancer patients.

Simple Sonochemical Method to Optimize the Heating Efficiency of Magnetic Nanoparticles for Magnetic Fluid Hyperthermia.

We developed a fast, single-step sonochemical strategy for the green manufacturing of magnetite (Fe3O4) magnetic nanoparticles (MNPs), using iron sulfate (FeSO4) as the sole source of iron and sodium hydroxide (Na(OH)) as the reducing agent in an aqueous medium. The designed methodology reduces the environmental impact of toxic chemical compounds and minimizes the infrastructure requirements and reaction times down to minutes. The Na(OH) concentration has been varied to optimize the final size and magnetic properties of the MNPs and to minimize the amount of corrosive byproducts of the reaction. The change in the starting FeSO4 concentration (from 5.4 to 43.1 mM) changed the particle sizes from (20 ± 3) to (58 ± 8) nm. These magnetite MNPs are promising for biomedical applications due to their negative surface charge, good heating properties (≈324 ± 2 W/g), and low cytotoxic effects. These results indicate the potential of this controlled, easy, and rapid ultrasonic irradiation method to prepare nanomaterials with enhanced properties and good potential for use as magnetic hyperthermia agents.

Determination of Liposomal Cisplatin by High-Performance Liquid Chromatography and Its Application in Pharmacokinetic Studies.

Liposomes have been employed as carriers for antineoplastic drugs to improve delivery. We describe an HPLC-UV method for determining cisplatin levels in liposomal and biological samples, which represents an attractive alternative to the widely used flame atomic absorption spectroscopy. Liposomal cisplatin was extracted from liposomes, plasma and tissue samples by using acetonitrile and separated on a Symmetry C18 column. The mobile phase was a mixture of water, methanol and acetonitrile, and detection was performed at 254 nm. The method was linear in the range of 0.5-10 µg/mL. Using this method, cisplatin concentration was measured in plasma, kidney, liver and tumor at different times post-administration of liposomal cisplatin. This method is proved suitable for measuring the levels of cisplatin encapsulated in a liposomal system, in plasma or tissue samples of experimental animals, after intravenous administration of liposomal cisplatin. Owing to the small plasma volume employed, a complete pharmacokinetic study can be done with a single animal.