Targeted drug-loaded PLGA-PCL microspheres for specific and localized treatment of triple negative breast cancer.

The paper presents the results of the experimental and analytical study of targeted drug-loaded polymer-based microspheres made from blend polymer of polylactic-co-glycolic acid and polycaprolactone (PLGA-PCL) for targeted and localized cancer drug delivery. In vitro sustained release with detailed thermodynamically driven drug release kinetics, over a period of three months using encapsulated targeted drugs (prodigiosin-EphA2 or paclitaxel-EphA2) and control drugs [Prodigiosin (PGS), and paclitaxel (PTX)] were studied. Results from in vitro study showed a sustained and localized drug release that is well-characterized by non-Fickian Korsmeyer-Peppas kinetics model over the range of temperatures of 37 °C (body temperature), 41 °C, and 44 °C (hyperthermic temperatures). The in vitro alamar blue, and flow cytometry assays in the presence of the different drug-loaded polymer formulations resulted to cell death and cytotoxicity that was evidence through cell inhibition and late apoptosis on triple negative breast cancer (TNBC) cells (MDA-MB 231). In vivo studies carried out on groups of 4-week-old athymic nude mice that were induced with subcutaneous TNBC, showed that the localized release of the EphA2-conjugated drugs was effective in complete elimination of residual tumor after local surgical resection. Finally, ex vivo histopathological analysis carried out on the euthanized mice revealed no cytotoxicity and absence of breast cancer metastases in the liver, kidney, and lungs 12 weeks after treatment. The implications of the results are then discussed for the development of encapsulated EphA2-conjugated drugs formulation in the specific targeting, localized, and sustain drug release for the elimination of local recurred TNBC tumors after surgical resection.

Protein C as an early biomarker to distinguish pneumonia from sepsis.

PURPOSE: Patients with pneumonia often are unrecognized as also having sepsis. We evaluated protein C, as a potential biomarker, to differentiate between patients with pneumonia and sepsis. MATERIALS AND METHODS: A retrospective chart review was performed for all protein C tests over a 14-month period (January 11, 2007, to March 10, 2008) at an 8-hospital system with 1706 total beds. Charts were screened for the discharge diagnoses of sepsis, severe sepsis, septic shock, bacteremia, and pneumonia. Protein C levels were compared between patients with sepsis and pneumonia, and at time intervals of 0 to 12 hours, 12 to 24 hours, 24 to 48 hours, and more than 48 hours after diagnosis. RESULTS: One thousand forty-seven protein C levels were obtained in 980 patients. Thirty-two protein C levels met the inclusion and exclusion criteria for the sepsis group, and 34 for the pneumonia group. Overall, the mean protein C levels were significantly less in patients with sepsis at 59.2% (95% confidence interval [CI], 49.5%-68.9%) compared with patients with pneumonia at 108.9% (95% CI, 95.6%-122.3%; P < .001). In addition, levels within each of the time intervals were also significantly lower in the sepsis group. CONCLUSIONS: In this study, protein C levels performed well in differentiating between patients with sepsis or pneumonia in the early period after diagnosis.