Fabrication and in vitroevaluation of silk fibroin-folic acid decorated paclitaxel and hydroxyurea nanostructured lipid carriers for targeting ovarian cancer cells: A double sword approach

Ovarian cancer (OC) is the most fatal gynecologic cancer, accounting for around 4% of cancer incidence globally. The conventional treatment plan for OC is systemic chemotherapy, which is usually followed after the standard surgical staging and cytoreduction. Currently, carboplatin, paclitaxel (PTX), or carboplatin and PTX are used as first-line therapies. The conventional approach has its own disadvantages, such as systemic toxicities, a subsequent relapse of the disease, nausea, hair loss, and a decline in plasma cell counts. In this study, to overcome the drawbacks of conventional chemotherapy, PTX-loaded NLCs (PTX NLCs) and hydroxyurea-loaded NLCs (HU NLCs) were prepared. Silk fibroin-folic acid conjugate was synthesized and decorated over these NLCs (SF-FA NLCs). These SF-FA NLCs were characterized and investigated as targeted drug delivery systems. In vitrocell cytotoxicity studies, cell cycle arrest, apoptosis studies and scratch assay were performed on SKOV-3 cell lines. These NLCs showed smaller particle size, good entrapment efficiency and were spherical in shape. The drug release was in sustained manner. The drug release followed first-order kinetics and fickian diffusion. These NLCs showed better cytotoxicity towards human ovarian cancer SKOV-3 cells when compared to pure paclitaxel. From flow cytometry cell cycle arrest, it was observed that the combination of these two drugs loaded NLCs (PTX and HU SF-FA NLCs) significantly inhibited SKOV-3 cells at G0/G1 and S phase. Results from apoptosis studies revealed that these NLCs had better apoptotic activity when compared to pure paclitaxel. Likewise, the nano-formulation had better inhibition of SKOV-3 cell proliferation compared to pure paclitaxel, which was confirmed from the scratch assay. Thus, from these results, we conclude that PTX and HU SF-FA NLCs may be promising drug delivery platforms for delivering PTX and HU to ovarian cancer cells.