Characterization of Betulinic Acid-Multiwalled Carbon Nanotubes Modified with Hydrophilic Biopolymer for Improved Biocompatibility on NIH/3T3 Cell Line.

The biocompatibility of carbon nanotubes (CNT) is fairly a challenging task for their applications in nanomedicine. Therefore, the objective of this research was to formulate four types of highly biocompatible betulinic acid-loaded biopolymer nanocomposites, namely chitosan-multiwalled carbon nanotubes (MWBA-CS), polyethylene glycol-multiwalled carbon nanotubes (MWBA-PG), Tween 20-multiwalled carbon nanotubes (MWBA-T2) and Tween 80-multiwalled carbon nanotubes (MWBA-T8). The physico-chemical properties of the modified nanocomposites were determined by Fourier transform infrared spectroscopy (FTIR), thermal analysis (TGA) and Raman spectroscopy, while the surface morphology of the resulting nanocomposites was studied using field emission scanning electron microscopy (FESEM). All data revealed that the external surface of MWBA nanocomposites was successfully coated with the respective polymer molecules through hydrophobic and electrostatic interactions with improved thermal profiles. The cell viability assay, which was performed on cultured normal embryonic mouse fibroblast cells, confirmed their excellent biocompatibility in phosphate-buffered saline aqueous media. Overall, our findings herein suggest that the synthesized biopolymer-coated MWBA nanocomposites are promising nanomaterials for drug delivery applications as they enhance the solubility and dispersibility of CNT with significantly reduced cytotoxic effect, especially in normal cells.

Preparation, characterisation and biological evaluation of biopolymer-coated multi-walled carbon nanotubes for sustained-delivery of silibinin.

This research work represents the first major step towards constructing an effective therapeutic silibinin (SB) in cancer treatment using oxidised multi-walled carbon nanotubes (MWCNT-COOH) functionalised with biocompatible polymers as the potential drug carrier. In an attempt to increase the solubility and dispersibility of SB-loaded nanotubes (MWSB), four water-soluble polymers were adopted in the preparation process, namely polysorbate 20 (T20), polysorbate 80 (T80), polyethylene glycol (PEG) and chitosan (CHI). From the geometry point of view, the hydrophobic regions of the nanotubes were loaded with water-insoluble SB while the hydrophilic polymers functionalised on the outer surfaces of the nanotubes serve as a protective shell to the external environment. The chemical interaction between MWSB nanocomposites and polymer molecules was confirmed by Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy. Besides, high-resolution transmission electron microscopy (HR-TEM), field emission scanning electron microscopy (FESEM), thermogravimetric analysis (TGA) and UV-visible spectrophotometry were also employed to characterise the synthesised nanocomposites. The morphological study indicated that the polymers were deposited on the external surfaces of MWSB and the nanocomposites were seen to preserve their tubular structures even after the coating process was applied. The TGA results revealed that the incorporation of biopolymers practically improved the overall thermal stability of the coated MWSB nanocomposites. Evaluation of the in vitro effect on drug release rate by the nanocomposites was found to follow a biphasic release manner, showing a fast release at an initial stage and then a sustained-release over 2500 min. Besides, the drug release mechanisms of the nanocomposites demonstrated that the amount of SB released in the simulated environment was governed by pseudo-second order in which, the rate-limiting step mainly depends on diffusion of drug through chemisorption reaction. Finally, MTT assay showed that the coated MWSB nanocomposites on 3T3 cells were very much biocompatible at a concentration up to 100 g/mL, which is an evidence of MWSB reduced cytotoxicity.

Incorporation of Levodopa into Biopolymer Coatings Based on Carboxylated Carbon Nanotubes for pH-Dependent Sustained Release Drug Delivery.

Four drug delivery systems were formulated by non-covalent functionalization of carboxylated single walled carbon nanotubes using biocompatible polymers as coating agent (i.e., Tween 20, Tween 80, chitosan or polyethylene glycol) for the delivery of levodopa, a drug used in Parkinson's disease. The chemical interaction between the coating agent and carbon nanotubes-levodopa conjugate was confirmed by Fourier transform infrared (FTIR) and Raman studies. The drug release profiles were revealed to be dependent upon the type of applied coating material and this could be further adjusted to a desired rate to meet different biomedical conditions. In vitro drug release experiments measured using UV-Vis spectrometry demonstrated that the coated conjugates yielded a more prolonged and sustained release pattern compared to the uncoated conjugate. Cytotoxicity of the formulated conjugates was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using normal mouse embryonic fibroblast 3T3 cell line. Compared to the non-coated conjugate, the MTT data indicated that the coating procedure improved the biocompatibility of all systems by 34⁻41% when the concentration used exceeded 100 µg/mL. In conclusion, the comprehensive results of this study suggest that carbon nanotubes-based drug carrier coated with a suitable biomaterial may possibly be a potential nanoparticle system that could facilitate drug delivery to the brain with tunable physicochemical properties.

In vitro drug release characteristic and cytotoxic activity of silibinin-loaded single walled carbon nanotubes functionalized with biocompatible polymers.

In this paper, we demonstrate the preparation of silibinin-loaded carbon nanotubes (SWSB) with surface coating agents via non-covalent approach as an effective drug delivery system. The resulting surface-coated SWSB nanocomposites are extensively characterized by Fourier transform infrared (FTIR) and Raman spectroscopies, ultraviolet-visible (UV-Vis) spectrometry and field emission scanning electron microscopy (FESEM). The FTIR and Raman studies show that an additional layer is formed by these coating agents in the prepared nanocomposites during the coating treatment and these results are confirmed by FESEM. Drug loading and release profiles of the coated SWSB nanocomposites in phosphate buffered saline solution at pH 7.4 is evaluated by UV-Vis spectrometry. The in vitro results indicate that the surface-modified nanocomposites, with SB loading of 45 wt%, altered the initial burst and thus, resulted in a more prolonged and sustained release of SB. In addition, these nanocomposites exhibit a pseudo-second-order release kinetic which was driven by the ion exchange between the ionized SWSB and the anions in the release medium. The cytotoxicity effect of the resulting nanocomposites on normal mouse fibroblast cells is evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It is observed that the surfactant and polymer coating improved the biocompatibility of the SWSB nanocomposites significantly, which deem further exploitation for their application as potential anticancer drug delivery system.