The objective of this study was to develop chitosan (CS) nanoparticles (NPs) loaded with deferoxamine mesylate (DFO) for slow release of this iron-chelating drug. Drug nanoencapsulation was performed via ionic gelation of chitosan using sodium tripolyphosphate (TPP) as cross-linker. Nanoparticles with a size ranging between 150 and 400 nm were prepared for neat CS/TPP with a 2/1 molar ratio while their yield was directly dependent on the applied stirring rate during the preparation process. DFO at different content (20, 45 and 75 wt %) was encapsulated into these nanoparticles. We found that drug loading correlates with increasing DFO content while the entrapment efficiency has an opposite behavior due to the high solubility of DFO. Hydrogen-bonding between amino and hydroxyl groups of DFO with reactive groups of CS were detected using FT-IR spectroscopy while X-ray diffraction revealed that DFO was entrapped in amorphous form in the CS nanoparticles. DFO release is directly dependent on the content of loaded drug, while model analysis revealed that the release mechanism of DFO for the CS/TPP nanoparticles is by diffusion. Treatment of murine RAW 264.7 macrophages with nanoencapsulated DFO promoted an increased expression of transferrin receptor 1 (TfR1) mRNA, a typical homeostatic response to iron deficiency. These data provide preliminary evidence for release of pharmacologically active DFO from the chitosan nanoparticles.Pharmaceutics 2020, 12, 238 2 of 17 the aid of a portable infusion pump at least 4-5 days per week and for 8-10 h each time. This rather strenuous procedure reduces compliance and compromises of quality of life.Nanocarriers, such as biocompatible polymers, offer unique possibilities to overcome cellular barriers and improve drug delivery [2]. Their small sizes allow high diffusivity across membranes improving drug permeability. Nanoparticles (NPs) have a diameter of less than 200 nm and this can facilitate their cellular uptake via receptor-mediated endocytosis, fluid phase endocytosis or even passive diffusion; moreover the small size reduces their clearance by the mononuclear phagocyte system, which in turn increases their circulation time in blood [3][4][5][6]. Thus, the encapsulation of DFO in biocompatible nanoparticles aiming in a slower and more controlled release of the drug in the blood could provide an alternative means for drug administration, bypassing the compliance issue and improving quality of life. Released DFO should maintain its pharmacological properties, efficacy and safety profile.Chitosan (CS) NPs have attracted a lot of attention as drug delivery vehicles due to their ability to protect the drug from degradation, to achieve higher drug-loading and to release it in a slow and sustained manner [7][8][9][10]. Furthermore, due to the hydrophilic properties of chitosan, CS NPs are suitable carriers for hydrophilic drugs, like DFO. Lately, CS NPs have shown promising results in delivering drugs for treatment of diabetes and cancer [11]. In another case, CS NPs were inoculated...
Herein, original magnetic drug delivery nanomaterials for cancer therapy are developed and compared, with the purpose to show active control over drug release by using an alternative magnetic field (AMF). The rationale is to combine polymers and superparamagnetic nanoparticles to trigger such drug release under AMF. Two magnetic nanosystems are thus presented: magnetic nanogels made of thermosensitive and biocompatible polymers and core-shell nanoparticles with a magnetic core and a molecularly imprinted polymer as shell. Both encapsulate doxorubicin (DOX) and the DOX controlled release was investigated in vitro and in cells under AMF excitation. It confirms that the local heat profile at the vicinity of the iron oxide core can be used for the DOX controlled release. It also shows that both nanosystems help delivering more DOX inside the cells compared to internalization of free DOX. Finally, the DOX intracellular release could be remotely triggered under AMF, in athermal conditions, thus enhancing DOX cytotoxicity.
In the present study, poly(ethylene furanoate) (PEF) and its nanocomposites with SiO 2 and TiO 2 have been prepared and studied. Emphasis is given to study the effect of different nanoadditives, time, and temperature on solid state polymerization (SSP) of PEF. SSP is conducted at 180, 190, and 200 °C for 1, 2, 3.5, and 5 h under vacuum application. From intrinsic viscosity ([η]) measurements it is found that in all SSP samples the molecular weight increase is time and temperature dependent. The addition of nanofillers results in polymer production with slightly higher average molecular weight, especially at lower temperatures. A simple kinetic model is also developed and used to predict the time evolution of polymer's [η], as well as the carboxyl and hydroxyl content during the SSP. From the experimental measurements and the theoretical simulation it is proved that the presence of the nanoadditives results in higher transesterification kinetic rate constants. Moreover, compared to poly(ethylene terephthalate) (PET), the lower [η] of PEF, results in a much higher number of hydroxyl end groups and larger tranesterification and esterification reaction rates. Finally, the activation energy for the transesterification of PEF is found to be much higher compared to that of PET.
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