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  • Title: Solanesol derived therapeutic carriers for anticancer drug delivery.
    Author: Xiong Y, Hou T, Liu L, Peng W, Wang C, Lu Y, Wang S, Shi J, Song S.
    Journal: Int J Pharm; 2019 Dec 15; 572():118823. PubMed ID: 31715346.
    Abstract:
    Metabolites of a large number of inert drug carriers can cause long-term exogenous biological toxicity. Therefore, carriers with simultaneous therapeutic effects may be a good choice for drug delivery. Herein, a series of pharmacologically active solanesol derivatives were synthesized and investigated for use as micellar drug carriers for cancer therapy. Solanesyl thiosalicylic acid (STS) was first synthesized by introducing a thiosalicylic acid group to solanesol, inspired by the characteristic structure of farnesyl thiosalicylic acid (FTS) which is a non-toxic inhibitor of all active forms of the RAS protein. Then, two amphiphilic derivatives of STS were formed with ester- and hydrazone (HZ)-bond linked methyl poly(ethylene glycol)(mPEG), mPEG-STS and mPEG-HZ-STS, respectively. The PEGylated STS could be formed stable nano-sized micelles loaded with Doxorubicin (DOX). In vitro, DOX loaded mPEG-STS and mPEG-HZ-STS micelles exhibited stronger tumor inhibition ability compared with free DOX. In vivo, blank mPEG-STS and mPEG-HZ-STS micelles showed an obvious inhibiting effect on tumor growth while the drug loaded micelles had the greatest tumor inhibition effect. The enhanced therapeutic effects and the synergistic effect observed with this solanesol-based drug delivery system could be attributed to the inherent therapeutic qualities of the drug carriers.
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