Encapsulation efficiency of single-walled carbon nanotube for Ifosfamide anti-cancer drug

Highlights

• Encapsulation efficiency of (10,10) armchair single-walled carbon nanotubes as a nanovectors have been investigated.

• The effects of Ifosfamide encapsulation on the electronic properties of the carbon nanotube studied.

• The atomic interactions of high polar IFO molecule and non-polar carbon nanotube, have been modeled.

Abstract

The encapsulation efficiency of (10,10) armchair single-walled carbon nanotubes as a nanovector for Ifosfamide anti-cancer drug has been investigated. (10,10) armchair single-walled carbon nanotube was selected because of larger inner volume for encapsulation, distinct inner and outer surfaces for functionalization and penetration possibility into cells or cell nucleus. Moreover, the adverse side effects of Ifosfamide can be reduced by single-walled carbon nanotubes. A complete understanding of the encapsulation process of drug molecules into carbon nanotubes is necessary for drug delivery development. All possible stable conformers of the drug have been investigated through geometry optimizations at the B3LYP/6-31G**level of theory by using the Gaussian 09 suite of programs and then encapsulation of the most stable conformer has been studied. Results show that the Ifosfamide drug molecule can be encapsulated into the internal cavity of armchair single-walled carbon nanotube. The corresponding adsorption energy is −3.87 eV. Furthermore, the effects of encapsulation on the electronic properties of the carbon nanotube such as equilibrium distances, HOMO–LUMO energy gap and DFT based descriptors have been also probed. Quantum mechanical calculations of encapsulation verify that a single-walled carbon nanotube could adsorb an Ifosfamide molecule spontaneously via the chemisorption process.

Introduction

Ifosfamide (IFO), 3-(2-Chloroethyl)-2-[(2-chloroethyl) amino] tetrahydro-2H-1,3,2- oxazaphosphorine -2-oxide, that was first developed at Asta-Werke in Germany, is one of the oxazaphosphorine class of alkylating agents that exhibits antitumor and immunomodulatory activities. Ifosfamide clinical activity in various cancers has been verified. Its dose-limiting toxicity is due to biotransformation that leads to highly reactive metabolites such as acrolein and chloroacetaldehyde. Healthy rapid dividing cells could be targeted to chemotherapy drugs to cause systemic toxicity for patients. But a high administered dosage has been resulted in high neurotoxicity, nephrotoxicity, urotoxicity, encephalopathy and cardiotoxicity [1].

Nanomaterials have been increasingly investigated in the biomedical field [[2], [3], [4], [5]]. Recent researches in nano encapsulation have provided drug delivery systems that increase the efficacy, specificity and targeting ability of therapeutic agents [[6], [7], [8]]. Nanocapsules with efficient drug molecule loading could reduce systemic toxicity and enhance the accumulation of drug at the target site. On the one hand, adverse side effects will be reduced and healthy normal cells will be protected from chemotherapy treatment. On the other hand, the drug could be protected from environmental impacts [[9], [10], [11]] by nano encapsulation until they reach the target site that results in long-term stability [12].

Carbon nanotubes (CNT), which are novel inflexible non-polar candidates for encapsulation, first discovered by Ijima in 1991 [13]. They show promising environmental [10], biological [14] and medical [15] applications. They offer excellent characteristics due to mechanical strength, high chemical stability and electrical properties [[16], [17], [18], [19]]. They could often be taken up by cells without the immune system recognition due to their small size and high aspect ratio. Carbon nanotubes with large accessible inner volume and open ends could be a promising alternative nanocarrier [[20], [21], [22], [23]]. Spontaneous encapsulation of biomolecules and drugs into the inner space of CNTs have been reported [12]. Functionalization, toxicity of CNTs and pharmacology are the most important limitation of carbon nanotubes in biological and biomedical environments which should be overcome. Surface modification with different hydrophilic molecules and other agents may increase the biocompatibility and water solubility of CNTs. Physical and chemical properties of armchair carbon nanotubes such as size, shape, aggregation, chemical composition, functionalization and solubility could be better improved. As a result, the biodistribution and pharmacokinetics made them soluble and biocompatible, so they may enter the cell nucleus. The drug can be attached on the external or the internal surface. Encapsulation or internalization depends on van der Waals forces and other weak interactions. However, encapsulation is sensitive to external environments [24].

SWNT-based drug delivery systems (DDS) have been widely developed. DDS could recognize specific receptors on the cancer cell surface and through specific interactions induce receptor-mediated endocytosis.

In this study, we have probed the interaction of the IFO molecule with a carbon nanotube as the drug carrier to reduce the adverse side effects and to produce a more effective drug delivery system. The atomic interactions of high polar IFO molecule and non-polar carbon nanotube have been modeled by density functional theory.