Background: We investigated the physicochemical properties of Medifoam® N and its wound healing performance compared to other commercially available polyurethane (PU) foam dressing in vitro and in vivo to gain insight in their clinical performance. Methods: Wound contact layer and cross-section of eleven polyurethane foam dressings were assessed with field-emission scanning electron microscope. Thickness, density, tensile strength, elongation, moisture-vapor transmission rate (MVTR), retention and absorptivity were measured to compare physical properties. Phosphate-buffered saline (PBS) solution absorption patterns were compared. An animal model for wound-healing was applied to validate in vitro findings. Results: Among eleven tested foam dressings, Medifoam® N has the smallest pore and cell sizes with excellent uniformity, i.e. it has 25 ~ 75 μm on the wound contact layer and 100 ~ 350 μm in the cross-section while other dressings have a larger pose size with larger variability. Compared to other PU foams, Medifoam® N also has moderate thickness, density, tensile strength, elongation and MVTR. Furthermore, it has excellent fluid absorption and retention capacity. These intrinsic properties of Medifoam® N contributed to improve fluid absorption patterns, i.e. other dressing material flawed out PBS solution on the dressings while Medifoam® N retained all the tested solutions. In animal wound-healing study, Medifoam® N treated animals showed excellent angiogenesis and collagen deposition even though epithelial recovery rate was not significantly different to other dressings. Conclusions: Medifoam® N has optimized physical properties and thus improved fluid absorption/retention capacity. Compared to other dressings, Medifoam® N showed excellent fluid absorption patterns and these characteristics contributed to improved wound healing and excellent angiogenic potential. We found that Medifoam® N showed the best results among the employed dressing samples.

Purpose: Epigallocatechin-3-gallate (EGCG) is an antioxidant agent derived from green tea. Because it has chemopreventive and anti-invasive effect against various cancer cells, EGCG can be used to inhibit proliferation and invasion of cholangiocarcinoma (CCA) cells. Methods: The anticancer effects of EGCG were studied using human CCA cells (HuCC-T1). Apoptosis was analyzed by Western blotting. Invasion and migration of cancer cells were assessed with Matrigel^® and wound healing assays. An animal tumor xenograft model of HuCC-T1 was used to study the in vivo antitumor activities of EGCG. Results: EGCG effectively inhibited the growth of HuCC-T1 cells with no adverse effects on the viability of 293T cells. EGCG induced apoptotic cell death at 5 µg/mL concentration. It inhibited the expression of mutant p53 and induced apoptotic molecular signals such as Bax/Bcl-2, Caspase, and cytochrome C. Furthermore, EGCG dose-dependently inhibited the activity of matrix metalloproteinase (MMP)-2/9, invasion, and migration. In the animal tumor xenograft model of HuCC-T1 cells, EGCG was subcutaneously administered beside the tumor for local treatment. EGCG efficiently inhibited growth of the tumor and suppressed carcinogenic molecular signals such as Notch1, MMP-2/9, and proliferating cell nuclear antigen. Conclusion: EGCG induced apoptosis of cancer cells without adverse effects on normal cells. EGCG inhibited growth, invasion, and migration of HuCC-T1 cells. We suggest EGCG as a promising candidate for local treatment of CCA.

Sorafenib-incoporated nanoparticles were prepared using a block copolymer that is composed of dextran and poly(DL-lactide-co-glycolide) [Dexb LG] for antitumor drug delivery. Sorafenib-incorporated nanoparticles were prepared by a nanoprecipitation-dialysis method. Sorafenib-incorporated Dexb LG nanoparticles were uniformly distributed in an aqueous solution regardless of the content of sorafenib. Transmission electron microscopy of the sorafenib-incorporated Dexb LG nanoparticles revealed a spherical shape with a diameter < 300 nm. Sorafenib-incorporated Dexb LG nanoparticles at a polymer/drug weight ratio of 40:5 showed a relatively uniform size and morphology. Higher initial drug feeding was associated with increased drug content in nanoparticles and in nanoparticle size. A drug release study revealed a decreased drug release rate with increasing drug content. In an in vitro anti-proliferation assay using human cholangiocarcinoma cells, sorafenib-incorporated Dexb LG nanoparticles showed a similar antitumor activity as sorafenib. Sorafenib-incorporated Dexb LG nanoparticles are promising candidates as vehicles for antitumor drug targeting.

Graft copolymer composed hyaluronic acid (HA) and poly(d,l-lactide-co-glycolide) (PLGA) (HAgLG) was synthesized for antitumor targeting via CD44 receptor of tumor cells. The carboxylic end of PLGA was conjugated with hexamethylenediamine (HMDA) to have amine end group in the end of chain (PLGA-amine). PLGA-amine was coupled with carboxylic acid of HA. Self-assembled polymeric micelles of HAgLG have spherical morphologies and their sizes were around 50–200 nm. Doxorubicin (DOX)-incorporated polymeric micelles were prepared by dialysis procedure. DOX was released over 4 days and its release rate was accelerated by the tumoric enzyme hyaluronidase. To assess targetability of polymeric micelles, CD44-positive HepG2 cells were employed treated with fluorescein isothiocyanate (FITC)-labeled polymeric micelles. HepG2 cells strongly expressed green fluorescence at the cell membrane and cytosol. However, internalization of polymeric micelles were significantly decreased when free HA was pretreated to block the CD44 receptor. Furthermore, the CD44-specific anticancer activity of HAgLG polymeric micelles was confirmed using CD44-negative CT26 cells and CD44-positive HepG2 cells. These results indicated that polymeric micelles of HaLG polymeric micelles have targetability against CD44 receptor of tumor cells. We suggest HAgLG polymeric micelles as a promising candidate for specific drug targeting.

Nanoparticles have been extensively investigated for targeted delivery of anticancer drugs. Since the folate receptor is universally over-expressed on the tumor cell membrane, folic acid is often used to modify the fate of nanoparticles in biologicals. To fabricate targetable nanoparticles, folic acid was conjugated to a pullulan backbone and poly(DL-lactide-co-glycolide) (PLGA) (abbreviated as FAPuLG) was conjugated. KB cells and NIH3T3-cell-bearing mice were prepared to prove folate receptor targeting of FAPuLG nanoparticles. Nanoparticles of FAPuLG copolymer that self-assembled in water were small with diameters <200 nm. Doxorubicin (DOX) as a model drug was incorporated into the FAPuLG nanoparticles that were used to treat folate receptor over-expressing KB human carcinoma cells. Fluorescence microscopy revealed that DOX-incorporated FAPuLG nanoparticles induced strong red fluorescence in the KB cells in the absence of folic acid. However, fluorescence intensity was decreased by blocking folate receptors. Antitumor activity of FAPuLG nanoparticles against KB cells in vitro was also decreased by blocking folate receptors. In animal study using near-infrared dye-conjugated FAPuLG nanoparticles, fluorescence intensity was significantly higher at KB solid tumor than that of NIH3T3. The results indicate that FAPuLG nanoparticles can target the folate receptor of tumor cells. FAPuLG nanoparticles are a promising candidate for active targeting of anticancer agents.