Enhancing the anti-ovarian cancer activity of quercetin using a self-assembling micelle and thermosensitive hydrogel drug delivery system

Abstract

Ovarian cancer, as one of the killers that threaten women's health, has been studied extensively. As a natural bioflavonoid with prospective effects, quercetin is highly recognized for its anti-cancer applications.However, one of the major challenges that quercetin faces is its poor water solubility, instability in physiological media, and subsequent poor bioavailability. Thus, optimizing the ideal drug delivery options is necessary to facilitate the harnessing of the maximum benefits from quercetin. In this study, a quercetin-loaded thermosensitive injectable hydrogel system (Qu-M-hydrogel composites) was constructed based on nanotechnology. Quercetin was encapsulated into MPEG-PCL (with a high drug loading of 7% and minor particle size of 32 nm) and then added into the blank thermosensitive hydrogel Pluronic F-127. The Qu-M-hydrogel composites showed a much slower release than Qu-M in vivo.Moreover, the cytotoxicity, apoptosis induction, and anti-tumor effects of the Qu-M-hydrogel composites on the abdominal SKOV-3 ovarian cancer mouse models were investigated in vivo. Compared with other groups, the Qu-M-hydrogel composites exhibited improved apoptosis induction and cell growth inhibition effects and in vivo trials showed a better balance between the anti-tumor efficacy in the Qu-M-hydrogel composite group than in other groups at an equal drug dose. In conclusion, the prepared Qu-M-hydrogel composites enhanced the anti-tumor activity by providing a high local quercetin concentration, sustained and stable drug release, extended drug retention inside the tumor, and low toxicity to normal tissues. The Qu-M-hydrogel composites might have great potential for clinical application in anti-ovarian cancer activity.

An insight into anticancer, antioxidant, antimicrobial, antidiabetic and anti-inflammatory effects of quercetin: a review

“…The formulated hydrogel system showed a slower release of quercetin in vivo. Qu-M–hydrogel composites showed enhanced apoptosis and inhibition of cell growth effects on the ovarian cancer mouse model (SKOV-3) [ 43 ].…”

Delivery of Natural Agents by Means of Mesoporous Silica Nanospheres as a Promising Anticancer Strategy

“…The factors affecting oral bioavailability are low absorption, extensive metabolism, and/or rapid elimination, in addition to low solubility and non-selective targeting of cancers. Several nanoplatform delivery systems focus on overcoming these challenges to introduce quercetin into clinical applications soon for cancer [362][363][364][365][366][367][368].…”

Quercetin and MicroRNA Interplay in Apoptosis Regulation in Ovarian Cancer

“…Further, the drug was retained inside the tumor mass for longer time periods which resulted in a high toxicity towards tumor cells with negligible effect on normal cells. Similarly, its growth inhibitory influence and ability for induction of apoptosis was significantly improved in vitro [32]. Additionally, the use of a thermosensitive hydrogel system could assist in overcoming the limitation of poor water solubility of quercetin, its destabilization in physiological media and hence its poor bioavailability [33,34].…”