Paclitaxel-Loaded Lipid-Coated Magnetic Nanoparticles for Dual Chemo-Magnetic Hyperthermia Therapy of Melanoma.

Melanoma is the most aggressive and metastasis-prone form of skin cancer. Conventional therapies include chemotherapeutic agents, either as small molecules or carried by FDA-approved nanostructures. However, systemic toxicity and side effects still remain as major drawbacks. With the advancement of nanomedicine, new delivery strategies emerge at a regular pace, aiming to overcome these challenges. Stimulus-responsive drug delivery systems might considerably reduce systemic toxicity and side-effects by limiting drug release to the affected area. Herein, we report the development of paclitaxel-loaded lipid-coated manganese ferrite magnetic nanoparticles (PTX-LMNP) as magnetosomes synthetic analogs, envisaging the combined chemo-magnetic hyperthermia treatment of melanoma. PTX-LMNP physicochemical properties were verified, including their shape, size, crystallinity, FTIR spectrum, magnetization profile, and temperature profile under magnetic hyperthermia (MHT). Their diffusion in porcine ear skin (a model for human skin) was investigated after intradermal administration via fluorescence microscopy. Cumulative PTX release kinetics under different temperatures, either preceded or not by MHT, were assessed. Intrinsic cytotoxicity against B16F10 cells was determined via neutral red uptake assay after 48 h of incubation (long-term assay), as well as B16F10 cells viability after 1 h of incubation (short-term assay), followed by MHT. PTX-LMNP-mediated MHT triggers PTX release, allowing its thermal-modulated local delivery to diseased sites, within short timeframes. Moreover, half-maximal PTX inhibitory concentration (IC50) could be significantly reduced relatively to free PTX (142,500×) and Taxol® (340×). Therefore, the dual chemo-MHT therapy mediated by intratumorally injected PTX-LMNP stands out as a promising alternative to efficiently deliver PTX to melanoma cells, consequently reducing systemic side effects commonly associated with conventional chemotherapies.

Magnetic nanoparticles and rapamycin encapsulated into polymeric nanocarriers.

PURPOSE: The objective of this study was to develop nanocapsules and nanospheres of polylactide-co-glycolide (PLGA) containing magnetic nanoparticles and rapamycin. METHOD: Magnetic nanoparticles (MP) were obtained by the co-precipitation of Fe(ll) and Fe(III) salts by addition of ammonium hydroxide. Nanocapsules (NC) and nanospheres (NS) containing either uncoated magnetic nanoparticles (MP), MP coated with oleic acid monolayer (MPOA) or MP coated with oleic acid bilayer (MPOA-OA) were prepared by the emulsion evaporation method. Rapamycin was also encapsulated into NC and NS. Morphology, size, size distribution, entrapment efficiency, stability and magnetization characteristics were determined. RESULTS: Non-contact AFM images showed that the composite nanoparticles were almost spherical in shape. The resulting polymeric nanocarriers were found to have a mean diameter of approximately 120 nm with a narrow size distribution. The influence of some experimental parameters on the entrapment efficiency and stability was determined. Nanocapsules and nanospheres prepared with uncoated magnetic nanoparticles exhibited higher entrapment efficiency and stability. Superparamagnetic behavior of the magnetic nanocomposite was demonstrated by magnetization data. These findings may contribute to the development of potential controlled release drug targeting devices based on magnetic polymeric nanocarriers.