Applications of carbon nanotubes in drug delivery

Barcelos, Karina de Almeida (2022) Applications of carbon nanotubes in drug delivery. Masters thesis, Memorial University of Newfoundland.

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Abstract

The latest carbon nanotubes (CNTs) applications and functionalities for disease treatment and diagnosis have been presented to further comprehend their role and significance in medicine. Recent CNTs-based approaches in therapeutical designs, biomedical engineering, regenerative medicine, biosensing and bioimaging have demonstrated various attractive possibilities for future people's health and quality of life enhancements, such as for cancer and infection therapies. Particularly for drug and gene delivery, these nanoparticles (NPs) have been studied extensively for transporting and translocating molecules into specific sites to attenuate undesired side effects and improve bioavailability and release efficiency of drugs, as well as physicochemical and biological properties of CNTs. We proposed a bioinspired, non-covalent CNTs functionalization strategy to augment their bioavailability and alleviate their biotoxicity. For functionalization, select amphiphilic peptides from a cytoskeletal biopolymer, microtubule (MT), were used. The peptides are involved in the MT polymerization by maintaining the essential lateral interactions among the MT’s α- and β-tubulin subunits. They also participate in forming the MT-binding sites for hosting several MT-targeting antimitotics. Utilizing in silico methods, this study showed the peptides influenced CNT’s diffusivity and aqueous solubility. The hydrodynamic shield formed by the peptides from β-tubulin was more widespread on the CNT than the α-tubulin peptides’; however, the latter created a broader hydrophobic CNT coating than those from the β-tubulin. In particular, the peptides consisting of the H1–B2, H10, H1–B2, and the M-loop, demonstrated structural features that serve to augment CNTs’ water solubility and dispersibility. The performance of the peptide-functionalized CNTs as drug carriers was examined by studying seventeen antimitotics. The CNT–peptides structural composition was identified as a suitable carrier for phomopsin A, laulimalide, epothilone A, epothilone D, discodermolide, eribulin, and docetaxel. The peptides played dual roles displaying affinities to the antimitotics and the CNT; in particular, the peptides from the H1–B2 and H2–B3 loops of β-tubulin exhibited exceptional binding properties. Specific mutations on the wildtype peptides, including those from the α-tubulin M-loop and H2–B3, or the β-tubulin H1–B2, are proposed to refine their hydrophobicity, eliminate unfavorable inter-peptides electrostatic interactions or the spatial hindrance at certain regions, to enhance their conformational steadiness and exposure to the tube surface. A combination of the select amphiphilic peptides from both tubulin subunits is suggested to improve CNTs bioavailability and efficiency for carrying insoluble hydrophobic cargos.

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