Fenretinide (4-HPR), as a semi-synthetic retinoid, has apoptosis-promoting effects as a single agent and chemotherapy synergist in vitro. When a human ovarian cancer cells line (A2780s) was treated with both PTX and 4-HPR, there was a synergistic anti-cancer effect demonstrated with a average combination index of 0.44. In this research, a new TPGS-Soluplus® mixed micelles were developed which encapsulation efficiencies of paclitaxel (PTX) and fenretinide (4-HPR) were as high as 98%, and the average diameter of the micelles was 66.26 nm. Cytotoxicity of the mixed micelles co-delivered with PTX and 4-HPR reduced significantly 7.3 and 25.1 times compared with free drug respectively in A2780s cells. More importantly, in vivo pharmacokinetic study, the loaded drugs in mixed micelles exhibited higher AUC and t_1/2 values than free drugs. Furthermore, in vivo antitumor efficacy experiments demonstrated that PF-TS exhibited superior in vivo antitumor activity on the inhibition rate of tumor growth than other treatment groups (77.8% corresponding tumor growth inhibition in PF-TS treated group vs 19.9, 12.5, and 26.0% of tumor growth inhibition rate in Taxol®, 4-HPR and Taxol®+4-HPR respectively). Therefore, the mixed micelles of co-deliver PTX and 4-HPR successfully constructed may hopefully be applied to the cancer combination treatment with less toxic effect and more antitumor activity.

Most antirheumatic drugs with high toxicity exhibit a narrow therapeutic window due to their nonspecific distribution in the body, leading to undesirable side effects and reduced patient compliance. To in response to these challenges, prodrug-based nanoparticulate drug delivery systems (PNDDS), which combines prodrug strategy and nanotechnology into a single system, resulting their many advantages, including stability for prodrug structure, the higher drug loading capacity of the system, improving the target activity and bioavailability, and reducing their untoward effects. PNDDS have gained attention as a method for relieving arthralgia syndrome of rheumatoid arthritis in recent years. This article systematically reviews prodrug-based nanocarriers for rheumatism treatment, including Nano systems based on prodrug-encapsulated nanomedicines and conjugate-based nanomedicines. It provides a new direction for the clinical treatment of rheumatoid arthritis.