Carbon Dot Cross-Linked Gelatin Nanocomposite Hydrogel for pH-Sensing and pH-Responsive Drug Delivery.

Delivery of therapeutics to the intestinal region bypassing the harsh acidic environment of the stomach has long been a research focus. On the other hand, monitoring a system's pH during drug delivery is a crucial diagnosis factor as the activity and release rate of many therapeutics depend on it. This study answered both of these issues by fabricating a novel nanocomposite hydrogel for intestinal drug delivery and near-neutral pH sensing at the same time. Gelatin nanocomposites (GNCs) with varying concentrations of carbon dots (CDs) were fabricated through simple solvent casting methods. Here, CDs served a dual role and simultaneously acted as a cross-linker and chromophore, which reduced the usage of toxic cross-linkers. The proposed GNC hydrogel sample acted as an excellent pH sensor in the near-neutral pH range and could be useful for quantitative pH measurement. A model antibacterial drug (cefadroxil) was used for the in vitro drug release study at gastric pH (1.2) and intestinal pH (7.4) conditions. A moderate and sustained drug release profile was noticed at pH 7.4 in comparison to the acidic medium over a 24 h study. The drug release profile revealed that the pH of the release medium and the percentage of CDs cross-linking influenced the drug release rate. Release data were compared with different empirical equations for the evaluation of drug release kinetics and found good agreement with the Higuchi model. The antibacterial activity of cefadroxil was assessed by the broth microdilution method and found to be retained and not hindered by the drug entrapment procedure. The cell viability assay showed that all of the hydrogel samples, including the drug-loaded GNC hydrogel, offered acceptable cytocompatibility and nontoxicity. All of these observations illustrated that GNC hydrogel could act as an ideal pH-monitoring and oral drug delivery system in near-neutral pH at the same time.

Magnetite (Fe3O4) nanocrystals affect the expression of genes involved in the TGF-beta signalling pathway.

An understanding of interaction of nanomaterials with living systems is fundamental to address nanosafety issues, which, in turn will dictate the future prospects of nanomedicine. Herein, we examine the molecular effects of uptake of Magnetite (Fe(3)O(4)) Nanocrystals (MNC) using a transcriptomics approach. The uptake of MNC was studied by electron microscopy. This was followed by transcriptional profiling using whole genome microarrays, functional analysis of microarray data, real time PCR and biochemical assay for CASP9. Transcriptional profiling revealed 69 genes to be differentially expressed upon MNC treatment. Many of these genes are associated with TGF-beta signaling and include ID1, ID2, ID3, CASP9, SMAD6 and SMAD7, which are important negative regulators of signaling pathways involved in development and tumorigenesis. Moreover, upon treatment with MNC, expression of CASP9 was also found to decrease in a dose dependent manner. This approach could help us to identify specific effects of MNC upon cells and give us simultaneous clues about their biocompatibility and therapeutic potential. The MNC can specifically interfere with TGF-beta signaling by inhibiting the expression of ID and SMAD genes. As TGF-beta signaling invokes different responses in undifferentiated cells and adult tissues in a cell-type specific manner, our findings have far reaching implications in cellular development, differentiation and cancer.