Evaluation of self-assembling properties of paclitaxel-biotin conjugates

Among many approaches to the creation of targeted chemotherapeutic agents, one relies on the attachment of biotin to the drug molecule. The prospect of such hybrid compounds has been demonstrated by the example of biotinylated taxane derivatives, in particular paclitaxel, which is widely used in clinical practice. However, the ability of paclitaxel-biotin conjugates to form self-assembled nanocomposites stable in aqueous media has not been revealed yet. Such a promising drug formulation would avoid the use of solubilizers often applied in conventional paclitaxel dosage forms and lead to side effects. In the present study the synthesis of paclitaxel-biotin conjugates differing in spacer chain length and hydrophobicity is described. It has been established that direct biotinylation of paclitaxel allows the resulting compound to form spherical nanoparticles. At the same time, the introduction of a hydrophilic spacer into the conjugate did not favor its ability to self-organize into such structures. It was demonstrated that the direct biotin-paclitaxel conjugate assembles into narrow-dispersed nanoparticles, which also have an optimal size (120–130 nm) for such drug delivery systems. Moreover, in the presence of non-toxic polyvinyl alcohol the nanoparticles were stable during storage. Taking into account also the ease of preparation, all these results make paclitaxel-biotin conjugate nanoparticles promising dosage forms based on paclitaxel derivatives.