Intravenous Administration of Dehydroxymethylepoxyquinomicin With Polymer Enhances the Inhibition of Pancreatic Carcinoma Growth in Mice.

BACKGROUND/AIM: Pancreatic cancer, which exhibits resistance to cytotoxic and molecular targeted drugs, has an extremely poor prognosis. Nuclear factor-κB (NF-κB) is constitutively activated in many pancreatic cancer cases. Although the NF-κB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) has exhibited anti-cancer effects in pancreatic cancer models, its poor solubility limits its use to intraperitoneal administration. MATERIALS AND METHODS: Poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB) forms stable polymer aggregates with DHMEQ. The stability of DHMEQ aggregated with PMB in the human blood was measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS) ex vivo. Anti-pancreatic cancer effects in AsPC-1 and MIA PaCa-2 pancreatic cancer cells were evaluated by cell growth inhibition assay in vitro and tumor growth inhibition assay in vivo. RESULTS: DHMEQ aggregated with PMB (PMB-DHMEQ) remained detectable after 60 min of incubation in the human blood, whereas DHMEQ aggregated with carboxymethyl cellulose (CMC-DHMEQ) was barely detectable. PMB-DHMEQ significantly inhibited AsPC-1 and MIA PaCa-2 cell growth in vitro compared to CMC-DHMEQ. Intravenous administration of PMB-DHMEQ reduced the tumor volume and liver metastasis compared to untreated or CMC-DHMEQ-treated mice. CONCLUSION: Aggregation with PMB improved the solubility of DHMEQ, and effectively inhibited pancreatic cancer cell growth both in vitro and in vivo.

Double-layered antibiotic-loaded cement spacer as a novel alternative for managing periprosthetic joint infection: an in vitro study.

BACKGROUND: Previous studies comparing antibiotic-loaded calcium phosphate cement to polymethylmethacrylate cement reported that although the former has higher elution volumes over a longer period, it is mechanically weak when used alone. To counter this problem, a double-layered antibiotic-loaded cement spacer in which calcium phosphate cement is coated with polymethylmethacrylate cement was created. METHODS: In this study, we compared the double-layered spacer to the polymethylmethacrylate cement spacer in terms of eluent antibiotic concentration, bioactivity against methicillin-resistant Staphylococcus aureus, and mechanical strength. Double-layered and polymethylmethacrylate cement spacers that were loaded with vancomycin (VCM) were prepared and immersed in phosphate buffer for 84 days. To facilitate VCM elution from calcium phosphate cores in double-layered spacers, we also drilled multiple holes into the calcium phosphate layer from the spacer surface. RESULTS: We found that VCM concentrations in double-layered spacer eluents were higher than those in polymethylmethacrylate cement spacer eluents. The double-layered spacer also had higher bioactivity than the polymethylmethacrylate cement spacer. Although the polymethylmethacrylate cement spacer eluent lost the ability to inhibit bacterial growth on day 56, the double-layered spacer eluent maintained this ability for the duration of our study. Finally, the double-layered spacer retained high mechanical strength throughout the study period. CONCLUSIONS: The beneficial biomechanical and drug-eluting properties of the double-layered spacer might qualify it to serve as a promising biomaterial that could be used for managing periprosthetic joint infections.