Co-Delivery of Curcumin and Paclitaxel by "Core-Shell" Targeting Amphiphilic Copolymer to Reverse Resistance in the Treatment of Ovarian Cancer.

BACKGROUND: Ovarian cancer is a common malignancy in the female reproductive system with a high mortality rate. The most important reason is multidrug resistance (MDR) of cancer chemotherapy. To reduce side effects, reverse resistance and improve efficacy for the treatment of ovarian cancer, a "core-shell" polymeric nanoparticle-mediated curcumin and paclitaxel co-delivery platform was designed. METHODS: Nuclear magnetic resonance confirmed the successful grafting of polyethylenimine (PEI) and stearic acid (SA) (PEI-SA), which is designed as a mother core for transport carrier. Then, PEI-SA was modified with hyaluronic acid (HA) and physicochemical properties were examined. To understand the regulatory mechanism of resistance and measure the anti-tumor efficacy of the treatments, cytotoxicity assay, cellular uptake, P-glycoprotein (P-gp) expression and migration experiment of ovarian cancer cells were performed. In addition, adverse reactions of nanoformulation to the reproductive system were examined. RESULTS: HA-modified drug-loaded PEI-SA had a narrow size of about 189 nm in diameters, and the particle size was suitable for endocytosis. The nanocarrier could target specifically to CD44 receptor on the ovarian cancer cell membrane. Co-delivery of curcumin and paclitaxel by the nanocarriers exerts synergistic anti-ovarian cancer effects on chemosensitive human ovarian cancer cells (SKOV3) and multi-drug resistant variant (SKOV3-TR30) in vitro, and it also shows a good anti-tumor effect in ovarian tumor-bearing nude mice. The mechanism of reversing drug resistance may be that the nanoparticles inhibit the efflux of P-gp, inhibit the migration of tumor cells, and curcumin synergistically reverses the resistance of PTX to increase antitumor activity. It is worth noting that the treatment did not cause significant toxicity to the uterus and ovaries with the observation of macroscopic and microscopic. CONCLUSION: This special structure of targeting nanoparticles co-delivery with the curcumin and paclitaxel can increase the anti-tumor efficacy without increasing the adverse reactions as a promising strategy for therapy ovarian cancer.

[Effects of pure total flavonoids from Citrus changshan-huyou on blood lipid metabolism in hyperlipidemic rats].

To observe and investigate the effects and mechanisms of the pure total flavonoids from Citrus changshan-huyou(PTFC) on blood lipid metabolism in hyperlipidemic rats. SD rats were fed with high fat diet for 4 weeks to induce hyperlipidemic rats model, meanwhile three dosages (50, 100, 200 mg•kg ⁻¹â€¢d ⁻¹) of PTFC were administrated intragastrically for 4 weeks respectively.After 2 weeks of modeling, their tail blood was taken and serum TC, TG, and HDL-C levels were detected by biochemical method and their body weight was measured. After 4 weeks of modeling, their body weight was measured and liver weight was measured, then the levels of TC, TG, HDL-C, LDL-C, ALT, AST, MDA and SOD in serum were detected to calculate lipid comprehensive index(LDL-C/HDL-C and LDL-C/TC ratios) and atherogenic index(AI); in addition, MDA and SOD levels were detected by biochemical method. The hitopathological changes of the liver tissues were observed by HE staining; the protein expression levels of PPAR-α, Lpl, and Lipc were detected by ELISA; and the mRNA expression levels of PPAR-α in the liver tissue were detected by Real-time PCR. The results showed that gavage administration of the PTFC significantly decreased the body weight, liver weight, liver index, serum ALT and AST activities, the levels of serum TC, TG, LDL-C, LDL-C/HDL-C, AI and increased serum HDL and LDL/TC level. Moreover, the PTFC significantly enhanced SOD activity and decreased the concentration of MDA in serum and liver tissue. Further mechanism investigation indicated that PTFC inhibited serum lipid accumulation by increasing the expressions PPAR-α, Lpl, Lipc protein and PPAR-α mRNA of the liver tissues. PTFC could actively regulate blood lipid metabolism by ameliorating hepatic function, improving the body's antioxidant capacity, lowering levels of oxidative stress, as well as positively regulating the expression levels of PPAR-α, Lpl, Lipc protein and PPAR-α mRNA of the liver tissues in rats.