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

Abstract 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. Graphical Abstrac

What Is in the Salad? Escherichia coli and Antibiotic Resistance in Lettuce Irrigated with Various Water Sources in Ghana

Introduction: Safety of the environment in which vegetables are grown, marketed and consumed is paramount as most are eaten raw. Irrigation sources include open drains and streams, which are often contaminated with human and animal waste due to poor sanitation infrastructure. In irrigated vegetable farms using such sources in Ghana, we assessed Escherichia coli counts, antibiotic resistance patterns and resistant genes on irrigated lettuce. Methods: A cross-sectional study was conducted between January–May 2022, involving five major vegetable farms in Ghana. Results: Escherichia coli was found in all 25 composite lettuce samples analyzed. Counts expressed in CFU/g ranged from 186 to 3000, with the highest counts found in lettuce irrigated from open drains (1670) and tap water using hose pipes (3000). Among all bacterial isolates, resistance ranged between 49% and 70% for the Watch group of antibiotics, 59% for the Reserved group and 82% were multidrug-resistant. Of 125 isolates, 60 (48%) were extended-spectrum beta-lactamase-producing, of which five (8%) had the blaTEM-resistant gene. Conclusions: Lettuce was contaminated with Escherichia coli with high levels of antibiotic resistance. We call on the Ghana Ministry of Food and Agriculture, Food and Drugs Authority and other stakeholders to support farmers to implement measures for improving vegetable safety

Etiology of Severe Acute Watery Diarrhea in Children in the Global Rotavirus Surveillance Network Using Quantitative Polymerase Chain Reaction

Background: The etiology of acute watery diarrhea remains poorly characterized, particularly after rotavirus vaccine introduction. Methods: We performed quantitative polymerase chain reaction for multiple enteropathogens on 878 acute watery diarrheal stools sampled from 14643 episodes captured by surveillance of children <5 years of age during 2013-2014 from 16 countries. We used previously developed models of the association between pathogen quantity and diarrhea to calculate pathogen-specific weighted attributable fractions (AFs). Results: Rotavirus remained the leading etiology (overall weighted AF, 40.3% [95% confidence interval {CI}, 37.6%-44.3%]), though the AF was substantially lower in the Americas (AF, 12.2 [95% CI, 8.9-15.6]), based on samples from a country with universal rotavirus vaccination. Norovirus GII (AF, 6.2 [95% CI, 2.8-9.2]), Cryptosporidium (AF, 5.8 [95% CI, 4.0-7.6]), Shigella (AF, 4.7 [95% CI, 2.8-6.9]), heat-stable enterotoxin-producing Escherichia coli (ST-ETEC) (AF, 4.2 [95% CI, 2.0-6.1]), and adenovirus 40/41 (AF, 4.2 [95% CI, 2.9-5.5]) were also important. In the Africa Region, the rotavirus AF declined from 54.8% (95% CI, 48.3%-61.5%) in rotavirus vaccine age-ineligible children to 20.0% (95% CI, 12.4%-30.4%) in age-eligible children. Conclusions: Rotavirus remained the leading etiology of acute watery diarrhea despite a clear impact of rotavirus vaccine introduction. Norovirus GII, Cryptosporidium, Shigella, ST-ETEC, and adenovirus 40/41 were also important. Prospective surveillance can help identify priorities for further reducing the burden of diarrhea