Electrospinning of Nanodiamond-Modified Polysaccharide Nanofibers with Physico-Mechanical Properties Close to Natural Skins.

Electrospinning of biopolymers has gained significant interest for the fabrication of fibrous mats for potential applications in tissue engineering, particularly for wound dressing and skin regeneration. In this study, for the first time, we report successful electrospinning of chitosan-based biopolymers containing bacterial cellulous (33 wt %) and medical grade nanodiamonds (MND) (3 nm; up to 3 wt %). Morphological studies by scanning electron microscopy showed that long and uniform fibers with controllable diameters from 80 to 170 nm were prepared. Introducing diamond nanoparticles facilitated the electrospinning process with a decrease in the size of fibers. Fourier transform infrared spectroscopy determined hydrogen bonding between the polymeric matrix and functional groups of MND. It was also found that beyond 1 wt % MND, percolation networks of nanoparticles were formed which affected the properties of the nanofibrous mats. Uniaxial tensile testing of the woven mats determined significant enhancement of the strength (from 13 MPa to 25 MP) by dispersion of 1 wt % MND. The hydrophilicity of the mats was also remarkably improved, which was favorable for cell attachment. The water vapor permeability was tailorable in the range of 342 to 423 µg·Pa(-1)·s(-1)·m(-1). The nanodiamond-modified mats are potentially suitable for wound healing applications.

Molecular Insights into the Loading and Dynamics of Doxorubicin on PEGylated Graphene Oxide Nanocarriers.

Molecular dynamics (MD) simulations were performed to investigate the loading and dynamics of doxorubicin (DOX) anticancer drug on graphene oxide (GO) and poly(ethylene glycol) (PEG) decorated GO (PEGGO) nanocarriers in an aqueous environment at human body temperature (310 K) and physiological pH level of 7.4. Mechanisms of DOX adsorption on PEGGO as a function of PEG chain length were revealed. While the total DOX-nanocarrier interaction energy was the same for the DOX/GO (control), DOX/Sh-PEGGO (short PEG chains consisting of 15 repeat units), and DOX/L-PEGGO (long PEG chains consisting of 30 repeat units) within the margin of error, the PEG-DOX interactions increased with an increase in the PEG chain length. At the same time, the PEG-DOX solvent-accessible contact area almost doubled going from the short to long PEG chains. PEGylation of the GO effectively causes an increase in the average water density around the nanocarrier, which can act as a barrier, leading to the DOX migration to the solvated PEG-free part of the GO surface. This effect is more pronounced for shorter PEG chains. The DOX-DOX solvent-accessible contact area is smaller in the DOX/GO system, which means the drug molecules are less aggregated in this system. However, the level of DOX aggregation is slightly higher for the PEGGO systems. The computational results in this work shed light on the fact that increasing the PEG chain length benefits DOX loading on the nanocarrier, revealing an observation that is difficult to acertain through experiments. Moreover, a detailed picture is provided for the DOX adsorption and retention in PEGGO drug delivery systems, which would enable the researchers to improve the drug's circulation time, as well as its delivery and targeting efficiency.

Doxorubicin Stability and Retention on PEGylated Graphene Oxide Nanocarriers Adjacent to Human Serum Albumin.

Drug stability and retention on nanocarriers is essential for maximizing the drug targeting and therapeutic efficiency. PEGylation of graphene oxide (GO) as a drug nanocarrier is widely known to prolong its circulation time in the body, thereby increasing the probability of drug delivery system interactions with the proteins in the blood stream. Herein, molecular dynamics (MD) simulations were performed to investigate the interactions between doxorubicin (DOX)-loaded GO and PEGylated GO (PEGGO) nanocarriers with human serum albumin (HSA), a prevalent human blood protein and among the first to be adsorbed on the DOX-loaded nanocarriers. The results indicate that drug stability and retention on PEGGO nanocarriers are far more superior to the GO nanocarriers (control) when in contact with HSA. It is also demonstrated in this work that the PEGGO nanocarriers retain the DOX molecules irrespective of the HSA Sudlow site I and II orientations, thereby revealing their robustness in DOX loading.

Molecular simulation of pH-dependent diffusion, loading, and release of doxorubicin in graphene and graphene oxide drug delivery systems.

In this study, the adsorption of doxorubicin (DOX), an anticancer drug, on pristine graphene (PG) and graphene oxide (GO) nanocarriers with different surface oxygen densities and in an aqueous environment with varying pH levels was investigated using molecular dynamics (MD) simulation. The drug loading and release on the GO nanocarrier was also simulated using pH as the controller mechanism. Overall, the DOX/nanocarrier interactions become stronger as the graphene surface oxygen density increases. Although pH has a negligible effect on the single-molecule drug adsorption on the GO surfaces under acidic and neutral conditions, significantly stronger DOX/nanocarrier interactions occur for the GO nanosheet with a lower surface oxygen density (GO-16, with an O/C ratio of 1 : 6) at basic pH levels. Moreover, the DOX/nanocarrier interactions are greatly weakened in the GO nanosheet with higher surface oxygen density (GO-13, with an O/C ratio of 1 : 3) under basic conditions. These observations are partly attributed to a more favorable geometry of the DOX molecule on the GO-16 surface as opposed to a loosely attached DOX molecule on the edges of the GO-13 nanosheet. When comparing the adsorption kinetics and transport properties of the DOX molecule in different GO systems, the drug diffusion coefficient increases with decreasing pH value (going from basic to neutral to acidic) due to the reduced total water-nanocarrier interactions. The latter observation is an indication of the more facilitated transport of the DOX molecule in an aqueous medium towards the nanocarrier surface at lower pH levels. Finally, we have confirmed the loading and release of the DOX molecules on the GO nanocarrier under neutral (pH = 7) and acidic (pH = 5) conditions, respectively. The former signifies the blood pH level, whereas the latter is reminiscent of the pH of a tumorous cell. The computational results presented in this work reveal the underlying mechanisms of DOX loading and release on PG and GO surfaces, which may be used to design better graphene-based nanocarriers for the DOX delivery and targeting applications.