Atrial Natriuretic Peptide Antibody-Functionalised, PEGylated Multiwalled Carbon Nanotubes for Targeted Ischemic Stroke Intervention.

Stroke is one of the major causes of disability and the second major cause of death around the globe. There is a dire need for an ultrasensitive detection tool and an effective and efficient therapeutic system for both detection and treatment of stroke at its infancy stage. Carbon nanotubes are promising nanomaterials for tackling these challenges. The loading of dexamethasone and decoration of PEGylated multiwalled carbon nanotube with atrial natriuretic peptide (ANP) antibody and fluorescein isothiocyanate for targeting ischemic site in the rat stroke model is presented here. Functionalisation of carbon nanotubes with dexamethasone (DEX), polyethylene glycol (PEG), fluorescein isothiocyanate (FITC), and ANP antibody caused a 63-fold increase in the D band intensity as illustrated by Raman. The characteristic band intensity increase was observed at 1636 nm following functionalisation of carbon nanotubes with polyethylene glycol and dexamethasone as confirmed by Fourier Transform Infrared. These findings have demonstrated the coupling capability of atrial natriuretic peptide antibody to DEX-PEG-CNTs. The baseline plasma atrial natriuretic peptide levels were ranging from 118 to 135.70 pg/mL prior to surgery and from 522.09 to 552.37 following common carotid artery occlusion. A decrease in atrial natriuretic peptide levels to 307.77 was observed when the rats were treated with FITC-DEX-PEG-ANP-CNTs, PEG-CNTs and DEX with a significant drop in the FITC-DEX-PEG-ANP-CNTs treated group. Fluorescence was detected in FITC-DEX-PEG-CNTs and FITC-DEX-PEG-ANP-CNTs treated ischemic stroke rats. The highest fluorescence intensity was reported in plasma (2179) followed by the kidney (1563) and liver (1507). These findings suggest a beneficial role that is played by the FITC-DEX-PEG-ANP-CNTs in the reduction of inflammation in the ischemic stroke induced rats that could induce a successful treatment of ischemic stroke.

Functionalized, Vertically Super-Aligned Multiwalled Carbon Nanotubes for Potential Biomedical Applications.

Currently, there is a lack of ultrasensitive diagnostic tool to detect some diseases such as ischemic stroke, thereby impacting effective and efficient intervention for such diseases at an embryonic stage. In addition to the lack of proper detection of the neurological diseases, there is also a challenge in the treatment of these diseases. Carbon nanotubes have a potential to be employed in solving the theragnostic challenges in those diseases. In this study, carbon nanotubes were successfully synthesized for potential application in the detection and treatment of the neurological diseases such as ischemic stroke. Vertically aligned multiwalled carbon nanotubes (VA-MWCNTs) were purified with HCl, carboxylated with H2SO4:HNO3 (3:1) and acylated with SOCl2 for use in potential targeting studies and for the design of a carbon-based electrode for possible application in the diagnosis of neurological diseases, including ischemic stroke. MWCNTs were washed, extracted from the filter membranes and dried in a vacuum oven at 60 °C for 24 h prior to functionalization and PEGylation. CNTs were characterized by SEM, TEM, OCA, DLS, CV and EIS. The HCl-treated CNT obtained showed an internal diameter, outer diameter and thickness of 8 nm, 34 nm and 75 µm, while these parameters for the H2SO4-HNO3-treated CNT were 8 nm, 23 nm and 41µm, respectively. PEGylated CNT demonstrated zeta potential, polydispersive index and particle size distribution of 6 mV, 0.41 and 98 nm, respectively. VA-MWCNTs from quartz tube were successfully purified, carboxylated, acylated and PEGylated for potential functionalization for use in targeting studies. For designing the carbon-based electrode, VA-MWCNTs on silicon wafer were successfully incorporated into epoxy resin for diagnostic applications. Functionalized MWCNTs were nontoxic towards PC-12 neuronal cells. In conclusion, vertically super-aligned MWCNTs have been successfully synthesized and functionalized for possible theragnostic biomedical applications in neurological disorders such as ischemic stroke.

Dexamethasone-Loaded, PEGylated, Vertically Aligned, Multiwalled Carbon Nanotubes for Potential Ischemic Stroke Intervention.

The complete synthesis, optimization, purification, functionalization and evaluation of vertically aligned multiwalled carbon nanotubes (VA-MWCNTs) was reported for potential application in dexamethasone delivery to the ischemic brain tissue. The conditions for high yield were optimized and carbon nanotubes functionalized and PEGylated prior to dexamethasone loading. Morphological changes were confirmed by SEM and TEM. Addition of functional groups to MWCNTs was demonstrated by FTIR. Thermal stability reduced following MWCNTs functionalization as demonstrated in TGA. The presence of carbon at 2θ of 25° and iron at 2θ of 45° in MWCNTs was illustrated by XRD. Polydispersive index and zeta potential were found to be 0.261 and −15.0 mV, respectively. Dexamethasone release increased by 55%, 65% and 95% in pH of 7.4, 6.5 and 5.5 respectively as evaluated by UV-VIS. The functionalized VA-MWCNTs were demonstrated to be less toxic in PC-12 cells in the concentration range from 20 to 20,000 µg/mL. These findings have demonstrated the potential of VA-MWCNTs in the enhancement of fast and prolonged release of dexamethasone which could lead to the effective treatment of ischemic stroke. More work is under way for targeting ischemic sites using atrial natriuretic peptide antibody in stroke rats.