Methods of packaging drugs

Exohedral fullerenes involve surface modifications on the outer surface of the fullerene, endohedral fullerenes include atoms, ions or other small drug molecules enclosed within the sphere of the molecule (IntechOpen, 2020).

In endohedral fullerenes, molecules are physically encapsulated within the structure, packaging the drug can be done in a few ways:

• The arc discharge method where a high voltage vaporizes graphite rods to fullerenes in a reaction environment with electropositive metals, the high heat forms the fullerene structure some of which may trap some of the metal atoms.
• Laser ablation is a similar method where a laser is used to vaporize graphite which condenses into fullerenes similarly trapping atoms.
• Molecular surgery involves chemically opening the fullerene to allow an atom or molecule to be inserted and then is sealed back through controlled reactions.
• Some endohedral fullerenes can be synthesized by heating graphite with metal oxides or nitrides in a nitrogen atmosphere to produce a fullerene with a metal nitride cluster encapsulated within it.

Exohedral fullerenes are modified by adding drug molecules or alternative functional groups to the fullerene surface, this can be done by:

• Covalent bonding (e.g. amide or ester bonds), where the pharmaceutical compound is attached directly to the fullerene. This allows for a more targeted and controlled release of the drug.
• Using molecular interactions like hydrogen bonding, pi-pi stacking or London forces. These methods allow fullerenes to self assemble which can improve their stability in biological environments.

How do the chemical properties of fullerenes make them suitable for drug delivery:

• Fullerenes have a large surface area allowing for the attachment of various functional groups allowing for a targeted delivery and higher biocompatibility. Their spherical structure allows for physical encapsulation, preventing degradation of the drug molecule.
• Fullerenes are good antioxidants and can be used to mop up cancerous free radicals in the body, an example of this is their potential use in photodynamic therapy where they are able to absorb lots of visible light and generate reactive oxygen species to kill cancerous tumour cells.
• In general c60 and c70 are the most commonly used forms of fullerenes for drug packaging due to their ability for encapsulation and relative stability, for example C60 (buckyballs) have to be heated up to 1000c to degrade.
• One of the problems with fullerenes is that they are inherently hydrophobic and require the functionalization by the addition of hydrophilic moieties (hydrophilic regions of a molecule) allowing them capability of water solubility for cellular delivery around the body. Fullerenes can also be placed in carriers such as micelles or liposomes to improve hydrophilicity.