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Measurement of ZnO nanoparticles using diffusive gradients in thin films: binding and diffusional characteristicsRapid growth in finding new applications for manufactured nanomaterials (MNM) has recently been accompanied by awareness about their related adverse toxicological and environmental impacts. Due to their intrinsic nature, measuring available concentrations of MNMs in the environment is a major challenge. This research is a launching point toward filling this gap, as it presents the potential of the well-established diffusive gradients in thin films (DGT) technique to determine MNMs concentrations in situ. Two binding layers commonly used in DGT devices were shown to be able to bind ZnO nanoparticles (ZnO NPs). The use of different types of diffusive layers demonstrated the critical role of their pore size for selective function of the DGT devices. The ZnO NPs can pass through the open pore diffusive layer used in standard DGT devices and be retained by the binding resin layer. However, the diffusion of ZnO NPs can be prevented when a 1000 MWCO (molecular weight cut off) dialysis membrane is placed in the front of the diffusive gel layer. A combination of two or more DGT devices with known diffusive layer properties should enable deduction of concentrations of available ZnO NPs in the environment. Unlike metal ions, determining diffusion coefficient values for ZnO NPs is challenging and greatly affected by shape, morphology, and solution-induced changes of the particles. Attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) demonstrated that retention of ZnO NPs by Chelex and Metsorb binding layers occurs through chemisorption. The superior uptake kinetic for Chelex indicates that it is a better candidate for further development of DGT devices to measure ZnO NPs. These initial results are promising and important for further developing the DGT technique to measure available concentrations of manufactured nanomaterials in the different environmental media (waters, soils, and sediments). Further experiments investigating the effects of pH, ionic strength, and solution chemistry on the performance of DGT for measuring MNM concentrations are needed.
Oral delivery of camptothecin using cyclodextrin/poly(anhydride) nanoparticlesCamptothecin (CPT), a molecule that shows powerful anticancer activity, is still not used in clinic due to its high hydrophobicity and poor active form's stability. In order to solve these drawbacks, the combination between poly(anhydride) nanoparticles and cyclodextrins was evaluated. CPT-loaded nanoparticles, prepared in the presence of 2-hydroxypropyl-β-cyclodextrin, (HPCD-NP) displayed a mean size close to 170nm and a payload of 50μg per mg (25 times higher than the one of the control nanoparticles). CPT was not released from nanoparticles under gastric conditions. However, under intestinal conditions, about 50% of the drug content was released as a burst, whereas the remained drug was released following a zero-order kinetic. Pharmacokinetic studies revealed that the CPT plasma levels, from orally administered nanoparticles, were high and sustained up to 48h. The CPT oral bioavailability was 7-fold higher than the value obtained with the control, whereas its clearance was significantly lower than for the aqueous suspension. These observations may be directly related to a prolonged residence time of nanoparticles in close contact with the intestinal epithelium, the presence of the cyclodextrin that decreases the CPT transformation into its inactive form and the generation of an acidic microenvironment during the degradation of the poly(anhydride) that would prevent the transformation of the active lactone into the inactive carboxylate conformation.
Self-assembly of pH-sensitive fluorinated peptide dendron functionalized dextran nanoparticles for on-demand intracellular drug delivery.In this study, the amphiphilic fluorinated peptide dendrons functionalized dextran (FPD-HZN-Dex) via an acid-sensitive hydrazone linkage was successfully designed and prepared for the first time. We demonstrated a spontaneous self-assembly of amphiphilic FPD-HZN-Dex into the well-defined nanoparticles with the core-shell architecture in aqueous media, which is attributed to the efficient amphiphilic functionalization of dextran by the hydrophobic fluorinated peptide dendrons. The spherical morphology, uniform particle size and good storage stability of the prepared FPD-HZN-Dex nanoparticles were characterized by dynamic light scattering and transmission electron microscopy, respectively. In vitro drug release studies showed a controlled and pH dependent hydrophobic drug release profile. The cell viability assays show excellent biocompatibility of the FPD-HZN-Dex nanoparticles for both normal cells and tumor cells. Moreover, the FPD-HZN-Dex self-assembled systems based on pH-sensitive hydrazone linkage also can serve as stimulus bioresponsive carriers for on-demand intracellular drug delivery. These self-assembled nanoparticles exhibit a stimulus-induced response to endo/lysosome pH (pH 5.0) that causes their disassembly over time, enabling controlled release of encapsulated DOX. This work has unveiled a unique non-covalent interaction useful for engineering amphiphilic dendrons or dendrimers self-assembled systems.