Effective intracellular release of ibuprofen triggered by thermosensitive magnetic nanocarriers.

Stimuli-responsive nanocarriers are being widely applied in the development of new strategies for the diagnosis and treatment of diseases. An inherent difficulty in general drug therapy is the lack of precision with respect to a specific pathological site, which can lead to toxicity, excessive drug consumption, or premature degradation. In this work, the controlled drug delivery is achieved by using magnetite nanoparticles coated with mesoporous silica with core-shell structure (MMS) and grafted with the thermoresponsive polymer poly [N-isopropylacrylamide-co-3-(trimethoxysilyl)propyl methacrylate] (MMS-P). The efficiency of MMS-P as a temperature-controlled drug delivery system was evaluated by in vitro release experiments using ibuprofen (IBU) in various mammalian cell models. Further, the effects of IBU as a photoprotectant in cells exposed to photodynamic therapy (PDT) in a carbaryl-induced neurodegenerative model were evaluated. The results showed that MMS-P nanocarriers do not exhibit cytotoxicity in HepG2 cells at high doses such as 7600 µg mL-1. Pre-incubation of MMS-P charged with IBU showed no effect on the PDT in N2A cells; however, it produced a further decrease in the viability of HepG2 cells, leading to a reduction to PDT resistance. On the other hand, a cytoprotective effect against carbaryl toxicity in N2A cells was observed in IBU administrated by MMS-P, which confirms the effective intracellular IBU uptake by means of MMS-P. These results encourage the potential application of MMS-P as a drug delivery system and confirm the effect of IBU as a cytoprotective agent in a neurodegenerative model.

Synthesis and in vitro testing of thermoresponsive polymer-grafted core-shell magnetic mesoporous silica nanoparticles for efficient controlled and targeted drug delivery.

In this work, thermoresponsive polymer grafted magnetic mesoporous silica nanoparticles were prepared, fully characterized and tested as controlled drug delivery systems. For this purpose, iron oxide nanoparticles coated with mesoporous silica shell were grafted with poly(N-isopropylacrylamide-co-3-(methacryloxypropyl)trimethoxysilane) (PNIPAM-co-MPS). The grafting and polymerization on the as-prepared nanoparticles were performed in one-step procedure. Using this methodology, the polymer was successfully grafted mainly onto the silica surface, leaving the mesopores empty for the drug loading. The prepared hybrid nanoparticles (MMSNP-PNIPAM-co-MPS) showed high magnetization saturation (19.5 emu g-1) and high specific surface area (505 m2 g-1) and pore volume (0.29 cm3 g-1). Ibuprofen was used as a model drug to test the performance of the hybrid particles as thermosensitive drug delivery systems. For this, in vitro drug delivery tests were conducted below (25 °C) and above (40 °C) the lower critical solution temperature (LCST) of the polymer (PNIPAM-co-MPS). Considerable difference (80%) in the ibuprofen release at these two temperatures and a fast and complete release of the drug at 40 °C was observed. These results suggest that the thermoresponsive copolymer acts as a gatekeeper for the temperature-controlled release of the drug loaded inside the mesopores. Therefore, MMSNP-PNIPAM-co-MPS are promising magnetic and thermoresponsive nanocarriers for targeted delivery of therapeutic substances.