Therapeutic efficacy of thermosensitive Pluronic hydrogel for codelivery of resveratrol microspheres and cisplatin in the treatment of liver cancer ascites.

Ascites constitutes the most frequent decompensating event in patients with advanced liver cancer and is associated with poor quality of life and high mortality. Intraperitoneal chemotherapy appears to be a reliable treatment strategy for advanced liver cancer ascites. However, the rapid metabolism of drugs and ascites dilution limits the efficacy of chemotherapeutics. Therefore, the present study aimed to develop a novel thermosensitive hydrogel drug system for targeted therapy of advanced hepatocellular carcinoma (HCC) ascites through intraperitoneal administration. The system was prepared by blending resveratrol (RES) microspheres and cisplatin (DDP) into thermosensitive Pluronic F127 hydrogel. The in vitro anti-tumor activity against H22 cells indicated that the prepared drug system could initiate apoptosis and induce cell cycle arrest at the G1 phase. The mice model of ascites with advanced HCC was established to validate the therapeutic potential of the F127 hydrogel drug system in vivo. The results revealed that intraperitoneal administration of F127 hydrogel drug could significantly inhibit the number of ascites, the proliferation of tumor cells, micro-angiogenesis, and prolong the survival of mice, thus, augmenting the efficacy of intraperitoneal chemotherapy. Moreover, immunohistochemical staining revealed that the F127 hydrogel drug system was safe and presented low toxicity to major vital organs. Collectively, this study highlights the clinical application potential of the F127 hydrogel drug delivery system.

In vitro and in vivo degradation behavior of n-HA/PCL-Pluronic-PCL polyurethane composites.

Scaffolds for bone tissue engineering applications should have suitable degradability in favor of new bone ingrowth after implantation into bone defects. In this study, degradation behavior of polyurethane composites composed of triblock copolymer poly(caprolactone)-poluronic-poly(caprolactone) (PCL-Pluronic-PCL, PCFC) and nanohydroxyapatite (n-HA) was investigated. The water contact angle and water absorption were measured to reveal the effect of n-HA content on the surface wettability and swelling behavior of the n-HA/PCFC composites, respectively. The weight loss in three degradation media with pH value of 4.0, 7.4, and 9.18 was also studied accordingly. Fourier transform infrared analysis, differential scanning calorimeter, X-ray diffraction, thermal-gravimetric analysis, and scanning electron microscopy were used to investigate the change of chemical structure and micromorphology after the n-HA/PCFC composite with 30% HA was degraded for different time intervals. Meanwhile, in vivo degradation was conducted by subcutaneous implantation. The weight loss and morphology change during observation periods were also studied.

Acceleration of dermal wound healing by using electrospun curcumin-loaded poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) fibrous mats.

This study prepared a composite scaffold composed of curcumin and poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) copolymer using coelectrospinning technology. Incorporation of curcumin into the polymeric matrix had an obvious effect on the morphology and dimension of PCEC/curcumin fibers. The results of in vitro anti-oxidant tests and of the cytotoxicity assay demonstrated that the curcumin-loaded PCEC fibrous mats had significant anti-oxidant efficacy and low cytotoxicity. Curcumin could be sustainably released from the fibrous scaffolds. More importantly, in vivo efficacy in enhancing wound repair was also investigated based on a full-thickness dermal defect model for Wistar rats. The results indicated that the PCEC/curcumin fibrous mats had a significant advantage in promoting wound healing. At 21 days post-operation, the dermal defect was basically recovered to its normal condition. A percentage of wound closure reached up to 93.3 ± 5.6% compared with 76.9 ± 4.9% of the untreated control (p < 0.05). Therefore, the as-prepared PCEC/curcumin composite mats are a promising candidate for use as wound dressing.

CXCL10 enhances radiotherapy effects in HeLa cells through cell cycle redistribution.

Radiotherapy is a crucial treatment for cervical cancer, the second most common type of cancer in women worldwide. In this study, we investigated the effects of CXC chemokine ligand 10 (CXCL10) gene therapy combined with radiotherapy on cervical cancer using HeLa cells. TUNEL assay revealed that the apoptotic rate in the combined treatment of CXCL10 gene therapy and radiotherapy was greatly increased compared with that of CXCL10 or radiotherapy alone. Flow cytometry showed that CXCL10 overexpression in HeLa cells resulted in a prolonged G1 phase and shortened S phase at 72 h post-transfection. Western blot analysis revealed that p27(Kip1) was up-regulated in CXCL10-treated HeLa cells; however, cyclin E was down-regulated. These results indicate that the combination of CXCL10 gene therapy and radiotherapy is an effective strategy for the growth suppression of HeLa cells, and that CXCL10 enhances the radiotherapy effects through cell cycle redistribution. Our data provide new insight into the treatment of cervical carcinoma, involving an effective combination of gene therapy and radiotherapy against tumors.