Nanosized Assemblies from Amphiphilic Solanesol Derivatives for Anticancer Drug Delivery.

Unexpected functionalities of pharmaceutical excipients have been found in some cases. Preplanned introduction of excipients with therapeutic effects might not only reduce the risks of metabolism-related toxicity but also provide synergistic therapeutic effects. Herein, natural original solanesol (SOL), one of the isoprene compounds with some pharmacological activities, was selected to prepare a series of amphiphilic derivatives by chemical modification, and drug delivery systems for oncotherapy were established. Three derivatives, including solanesyl bromide (SOL-Br), monosolanesolsolanesyl succinate (MSS), and solanesylthiosalicylate (STS), were synthesized and formulated into nanosized self-assemblies for doxorubicin (DOX) encapsulation. Meanwhile, polyethylene glycol (PEG) derivatives were synthesized as the stabilizer of solanesol-based self-assemblies, among which hydrazine-poly(ethylene glycol)-hydrazine (PEG6000-DiHZ) was found to be more reliable. The optimized molar ratio between PEG 6000 -DiHZ and solanesol derivatives was found to be 2:1, considering the drug-loading capacity of self-assemblies. Consistent release profiles were found for the DOX-loaded self-assemblies, in which about 75-80% DOX was cumulatively released within 60 h at pH 5.0. The three DOX-loaded self-assemblies were found to be homogeneous spheres with average particle sizes in the range of 100-200 nm by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Blank self-assemblies were found to have an inhibiting ability toward MCF-7 and HepG-2 cancer cells, which might originate from the inherent nature of solanesol derivatives. In vivo pharmacodynamic experiments demonstrated that blank self-assemblies had certain inhibitory effect on tumor growth compared with the controls. Further enhanced effects were also found for the drug-loaded self-assemblies due to the synergistic anti-tumor effect existing between the drug and the carriers. This work has presented a simple and effective strategy to prepare a therapeutic carrier by direct assembling of the therapeutic compound without PEGylation steps, by which the therapeutic carrier materials could take their effect directly and synergistically along with the loaded drugs.