Triple-negative breast cancer (TNBC) presents with resistance phenotypes to certain therapies, such as cisplatin, often requiring higher dosing, with associated acquired tumor resistance, renal toxicity, and variable patient responses. A self-emulsifying drug delivery (SEDD) formulation approach was proposed to overcome the limitations of cisplatin in TNBC, focusing on improving intracellular cisplatin and control siRNA uptake as a proof-of-principle of dual drug delivery. Four SEDD formulations were prepared and optimized for cisplatin (o/w) emulsion and FITC-siRNA (w/o) emulsion using pseudo-ternary phase diagrams to facilitate the formation of water-in-oil-water (w/o/w) emulsions. Formulations were characterized by size, polydispersity (PDI), and surface charge and tested in vitro. Cellular uptake via triplex staining of drug-loaded SEDDs was investigated. SEDDs showed enhanced internalization and promoted selective TNBC cellular uptake. The current study is a proof-of-principle for the successful co-delivery of cisplatin (small molecule) and siRNA (large molecule) via the SEDDs platform.

Objective. Faculty at MCPHS University’s School of Pharmacy, Worcester/Manchester are engaged in continuous quality improvement of their teaching and assessment methods to prepare students for successful careers in pharmacy. This study evaluated the impact of a formative mock exam on student performance in an actual summative exam (Exam) administered during the spring 2020 semester of a pharmaceutical calculations course. Methods. A retrospective analysis of student test scores in a summative assessment (Exam) was performed across two cohort years (2019 and 2020) where students were not administered and administered a formative mock exam, respectively. Central tendency and comparative analysis measures were performed to assess differences in student performance. Results. Out of 237 students enrolled, 221 students participated in the optional mock exam and all 237 students participated in the Exam, with average scores for the mock exam and the Exam being 67% and 94%, respectively. Ninety-two students who received grade C or better on their mock exam had an Exam average score (98%) that was significantly higher than those who received a D or F (n=129, 92%); and the average score in 2020 Exam was significantly higher when compared to the 2019 Exam where no mock exam was offered (94% versus 77%). Conclusion. This was a descriptive, cross-sectional study to understand the differences in student performance in a summative assessment across two cohort years with and without a formative mock assessment. The results demonstrated an association of the formative mock exam with better performance among students, without establishing a causal relationship.

Objectives: EGFR tyrosine kinase inhibitor (EGFR-TKI) therapies such as erlotinib and gefitinib are approved for the treatment of non-small cell lung cancer (NSCLC). However, the high incidence of acquired resistance to these EGFR-TKIs may preclude their effectiveness. Piperlongumine (PPL), an extract from the long pepper fruit (Piper longum), has been shown to possess anticancer properties. The purpose of the study was to investigate piperlongumine as an anticancer agent and to study a combination treatment approach with EGFR-TKIs against lung cancer cells. Methods: Anticancer efficacy of PPL, erlotinib (ERL), gefitinib (GEF), and cisplatin (CIS) were investigated in H1299 and H1975 cell lines. Cells were treated with PPL, ERL, GEF, and CIS alone, and in combination, cell viability was determined after 72 h. The mechanism of PPL-induced cytotoxicity was investigated via reactive oxygen species (ROS) induction, and apoptosis induction using acridine orange/ethidium bromide staining and flow cytometry. The effect of treatment on EGFR-mediated oncogenic signaling was investigated by immunoblotting for mitogenic and apoptotic markers. Results: PPL exhibited a potent cytotoxic effect in H1299 and H1975 cells compared to ERL, GEF, and CIS. Combination treatments of PPL with GEF and ERL showed significant reductions in cancer cells compared to control in both cell lines, which were associated with apoptotic induction, but without significant ROS induction. Compared to control, PPL with GEF significantly increased apoptotic cell death in H1975as confirmed with flow cytometry. Treatment with PPL alone and in combination induced anti-mitogenic and apoptotic responses at the molecular level. Conclusion: PPL sensitized lung cancer cells to EGFR-TKI and induced potent cytotoxic effects at low concentrations.

Background: Oral delivery of chemotherapeutic agents remains challenging due to gastrointestinal degradation, poor intestinal permeability, and extensive first-pass metabolism, which collectively limit bioavailability. Lipid-based drug delivery systems offer a promising strategy to overcome these barriers. This study aimed to develop a freeze-dried, solid-dispersible self-emulsifying drug delivery system (SEDDS) using a water-in-oil-in-water (w/o/w) double emulsion approach for the co-encapsulation of hydrophilic (doxorubicin) and lipophilic (ellipticine) agents to enhance oral delivery. Methods: Double-emulsion SEDDS were prepared via a two-stage emulsification process to enable compartmentalized drug loading within aqueous and oil phases. The formulations were freeze-dried to improve stability and storage. Physicochemical properties were characterized using dynamic light scattering for droplet size and polydispersity index (PDI), zeta potential analysis for colloidal stability, and differential scanning calorimetry for thermal behavior. Drug encapsulation efficiency was determined, and cellular uptake was evaluated in breast cancer cells using fluorescence microscopy. Results: Optimized SEDDS exhibited droplet sizes of 90–347 nm with low PDI values (0.005–0.336), indicating uniform and stable dispersions. Zeta potential values (−10.64 to 2.38 mV) supported colloidal stability, while freeze-dried formulations retained dispersion characteristics upon reconstitution over extended storage. Both drugs demonstrated high encapsulation efficiency (>97%), and thermal analysis confirmed the formation of stable amorphous systems. Fluorescence imaging revealed enhanced intracellular uptake of both agents. Conclusions: This study demonstrates that freeze-dried double-emulsion SEDDS enable efficient co-delivery of hydrophilic and lipophilic drugs, improving stability and cellular uptake. This platform shows strong potential for overcoming key barriers in oral chemotherapy and provides a promising strategy for combination drug delivery.

Objectives: The current treatment options and therapeutic targets for triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer (BrCA), are limited. This study aimed to identify novel biomarkers and transcriptional regulatory networks (TRN) inherent in TNBC samples. Methods: We analyzed pan-cancer BrCA datasets from The Cancer Genome Atlas (TCGA) to compare triple-positive breast cancer (TPBC) with TNBC. TRN algorithms and virtual inference of protein-enriched regulon (VIPER) were used to identify master regulators and their target genes. Utilizing TNBC cells (MDA-MB-231 and MDA-MB-468), we validated the relationship of nuclear factor erythroid 2-like 3 (NFE2L3) and basic helix-loop-helix family member E 40 (BHLHE40) by performing a luciferase assay. The expression levels of these targets were measured after transfections with plasmid and siRNA via qRT-PCR and western blots. The effect of these genes on cell proliferation and migration was studied using phenotypic assays. Results: Using computational approaches, we identified NFE2L3 as a master regulator with BHLHE40 as its target gene. NFE2L3 protein binds to the promoter region of BHLHE40 and regulates its transcriptional activity. Additionally, silencing and overexpressing NFE2L3 and BHLHE40 in TNBC cell lines MDA-MB-231 and MDA-MB-468 showed that NFE2L3 directly regulates BHLHE40 at both transcriptional and translational levels. We found that BHLHE40 requires NFE2L3 for cell proliferation and migration in TNBC. Conclusion: These findings underscore the significance of NFE2L3 and BHLHE40 in TNBC, highlighting NFE2L3’s role in regulating the oncogenic activity of BHLHE40 in TNBC cells.