Applications of carbon nanotubes in drug delivery

The development of new and efficient drug delivery systems is of fundamental importance to improve the pharmacological profiles of many classes of therapeutic molecules. Many different types of drug delivery systems are currently available. Within the family of nanomaterials, carbon nanotubes (CNT) have emerged as a new alternative and efficient tool for transporting and translocating therapeutic molecules. CNT can be functionalised with bioactive peptides, proteins, nucleic acids and drugs, and used to deliver their cargos to cells and organs. Because functionalised CNT display low toxicity and are not immunogenic, such systems hold great potential in the field of nanobiotechnology and nanomedicine.

Introduction

Carbon nanotubes (CNT) [1, 2, 3] are considered ideal materials for several applications [4], ranging from ultrastrong fibers [5] to field emission displays [6]. Recently, CNT have generated great interest in biology [7^•], where suitably modified CNT can serve as vaccine delivery systems [8] or protein transporters [9^•].

CNT can be imaginatively produced by rolling up a single layer of graphene sheet (single-walled CNT; SWNT) [10, 11], or by rolling up many layers to form concentric cylinders (multi-walled CNT; MWNT) [3] (Figure 1). As-produced CNT, both SW and MW, are commercially available, with different structural details and variable degrees of purity. Pristine CNT are completely insoluble in all solvents, which has generated some health concerns; consequently, their biological properties are being studied in terms of toxicity [12]. The development of efficient methodologies for the chemical modification of CNT has stimulated the preparation of soluble CNT that can be employed in several biological applications, among which drug delivery appears to be particularly promising [13•, 14, 15, 16].

Two functionalisation approaches are widely employed for modification of CNT (Figure 2). CNT can be oxidised using strong acids, resulting in the reduction of their length while generating carboxylic groups, which increase their dispersibility in aqueous solutions [17]. Alternatively, addition reactions to the CNT external walls and tips make them soluble in water [18, 19]. Solubility under physiological conditions is a key prerequisite to make CNT biocompatible. In addition, functionalised carbon nanotubes (f-CNT) can be linked to a wide variety of active molecules, including peptides, proteins, nucleic acids and other therapeutic agents.

An efficient way to functionalise the external walls of CNT is based on the 1,3-dipolar cycloaddition of azomethine ylides. CNT undergo the addition reaction when heated in DMF in the presence of an α-amino acid and an aldehyde [20]. The scope of this reaction is very broad and produces f-CNT that possess high solubility in a wide range of solvents. By carefully choosing the reactants, it is possible to modulate solubility in organic solvents or aqueous solutions [21^•]. CNT carrying ammonium groups (Figure 2b) are very soluble in water and have been exploited for their potential in the delivery of therapeutic molecules.

The biological applications of f-CNT are currently under intense investigation. In this paper we review the most recent achievements of CNT in drug delivery, with a specific emphasis on the work performed in our groups.