Читать книгу Magnetic Nanoparticles in Human Health and Medicine - Группа авторов - Страница 49

Liposomes represent one of the most investigated platforms for drug administration. These lipidic vesicles are stable, biocompatible, and their preparation is very well‐established. In this section, some examples of nanoparticle clustering obtained by the use of different lipids are described.

Martina et al. proposed one of the first examples of the inclusion of magnetic nanoparticles in lipidic vesicles. Aqueous maghemite NPs obtained by coprecipitation (and stabilized with a citrate capping) were mixed with egg‐yolk L‐α‐phosphatidylcholine (EPC) and 1,2‐diacyl‐SN‐glycero‐3‐phosphoethanolamine‐N‐[methoxy(poly(ethylene glycol))‐2000] (DSPE‐PEG2000), and unilamellar magnetic liposomes were prepared by thin‐film hydration method coupled with sequential extrusion. By this method, 200 nm liposomes were obtained, sterically stabilized by PEG chains and containing superparamagnetic maghemite particles whose concentration can be varied. Magnetophoresis confirmed the superparamagnetic profile and the effect of particles confinement into the vesicle core (Martina et al. 2005).

Ménager group reported the preparation of unilamellar magnetic liposomes by a different approach, namely reverse‐phase evaporation method. In this approach, an aqueous suspension of citrate‐coated magnetic nanoparticles and a chloroform solution of phospholipids (DPPC/DSPC/DSPE‐PEG 2000) were mixed and ultrasonicated to induce the formation of a nanoemulsion. Soon after, the organic solvent was removed by rotary evaporation, and the magnetic liposomes were dispersed in the remaining aqueous phase. After filtration (to discard liposomes with a size above 0.45 μm), nonmagnetic liposomes were removed after magnetic separation. By magnetophoresis, the volume fraction corresponding to magnetic nanoparticles (7 nm) into the liposome was estimated as 33% of total volume (Bealle et al. 2012). These magneto‐liposomes have been further developed for a multiple therapeutic application. A photosensitizer used in photodynamic therapy, namely the hydrophobic m‐THPC, was introduced into the lipidic bilayer of the liposomes. Thus, the multifunctional system was tested in vitro and in vivo for the application of a dual‐treatment, combining magnetic hyperthermia and laser‐assisted photodynamic therapy. A small dose of nanoclusters was intratumorally injected, and the mice were exposed to the noninvasive treatments for three consecutive days. The single‐treatment groups showed only a reduction of tumor volume and regrowth after seven days. The synergistic combination of magnetic hyperthermia and photodynamic therapy produced a total regression of tumoral tissue four days after injection, instead (Di Corato et al. 2015).

Amstad et al. suggested a different architecture for magnetic lipidic vesicle. In their work, the authors investigated the effects of iron oxide capping agents on the localization of NPs in the liposome. By using the traditional oleic acid‐capped NPs, an evident agglomeration of nanoparticles was obtained, and a micelle profile was preferred. By functionalizing the magnetic nanoparticles with palmityl‐nitroDOPA, a selective localization was achieved, with confinement in the lipidic bilayer, with a concentration of 10 wt %. Alternating magnetic fields were used to control timing and dose of repeatedly released cargo from this pegylated vesicles; the inducted local heating of the membranes caused a transient change of the permeability, without effect on the system structure (Amstad et al. 2011).

Nandwana et al. reported the preparation of lipidic nanocapsules with a peculiar hollow‐core structure. In details, these nanocapsules were obtained by an emulsion process of cationic lipids and water‐dispersed ferrites. As a result, a micellar architecture was obtained, with a hollow hydrophobic core, exploited for drug loading, and a hydrophilic surface, entirely decorated with a very high density of magnetic nanoparticles. Interestingly, the initial Mn–Zn ferrites, synthesized by thermal decomposition method, show a high r₂ relaxivity at 3 T (425 mM⁻¹ s⁻¹), and that what resulted even increased when the particles were confined in the nanocapsule structure (680 mM⁻¹ s⁻¹). These results were explained by the synergistic interactive magnetism between adjacent nanoparticles (Nandwana et al. 2018).

Salvatore et al. described the preparation of a sophisticated system based on the assembly of different building blocks: a DPPC‐based liposome, a ds‐DNA conjugated with a cholesteryl unit (that inserts spontaneously into the liposome membrane), hydrophobic iron oxide nanoparticles, and hydrophilic iron oxide@gold core‐shell nanoparticle (transferred in water by functionalization with a methoxy‐PEG and a thiolated oligonucleotide). By the sequential assembly of these blocks, a peculiar architecture was obtained, with hydrophobic particles embedded in the lipidic bilayer. In contrast, the core@shell nanoparticles were grafted on the liposome surface via interaction with ds‐DNA‐cholesteryl and subsequent insertion in the liposome. The liposome core was instead used as a carrier for a test payload. The authors demonstrated that the different confinement of these magnetic nanoparticles could be exploited for a sequential release of payload or oligonucleotide by just tuning into alternate magnetic field (AMF) impulses. In detail, 3.22 kHz AMF for five minutes provoked the release of the hydrophilic drug contained in the aqueous core of magnetoliposomes. Subsequently, the application of a 6.22 kHz AMF for 15 minutes induced the melting of DNA strands and the release of the zipper therapeutic oligonucletotide (Salvatore et al. 2016).