Development of a claims-based risk-scoring model to predict emergency department visits in older patients receiving anti-neoplastic therapy.

This study developed and validated a risk-scoring model, with a particular emphasis on medication-related factors, to predict emergency department (ED) visits among older Korean adults (aged 65 and older) undergoing anti-neoplastic therapy. Utilizing national claims data, we constructed two cohorts: the development cohort (2016-2018) with 34,642 patients and validation cohort (2019) with 10,902 patients. The model included a comprehensive set of predictors: demographics, cancer type, comorbid conditions, ED visit history, and medication use variables. We employed the least absolute shrinkage and selection operator (LASSO) regression to refine and select the most relevant predictors. Out of 120 predictor variables, 12 were integral to the final model, including seven related to medication use. The model demonstrated acceptable predictive performance in the validation cohort with a C-statistic of 0.76 (95% CI 0.74-0.77), indicating reasonable calibration. This risk-scoring model, after further clinical validation, has the potential to assist healthcare providers in the effective management and care of older patients receiving anti-neoplastic therapy.

Single enzyme nanoparticle, an effective tool for enzyme replacement therapy.

The term "single enzyme nanoparticle" (SEN) refers to a chemically or biologically engineered single enzyme molecule. SENs are distinguished from conventional protein nanoparticles in that they can maintain their individual structure and enzymatic activity following modification. Furthermore, SENs exhibit enhanced properties as biopharmaceuticals, such as reduced antigenicity, and increased stability and targetability, which are attributed to the introduction of specific moieties, such as poly(ethylene glycol), carbohydrates, and antibodies. Enzyme replacement therapy (ERT) is a crucial therapeutic option for controlling enzyme-deficiency-related disorders. However, the unfavorable properties of enzymes, including immunogenicity, lack of targetability, and instability, can undermine the clinical significance of ERT. As shown in the cases of Adagen®, Revcovi®, Palynziq®, and Strensiq®, SEN can be an effective technology for overcoming these obstacles. Based on these four licensed products, we expect that additional SENs will be introduced for ERT in the near future. In this article, we review the concepts and features of SENs, as well as their preparation methods. Additionally, we summarize different types of enzyme deficiency disorders and the corresponding therapeutic enzymes. Finally, we focus on the current status of SENs in ERT by reviewing FDA-approved products.

Chemosensitizing indomethacin-conjugated chitosan oligosaccharide nanoparticles for tumor-targeted drug delivery.

A chitosan oligosaccharide (CSO)-indomethacin (IDM) conjugate (CI) was synthesized to fabricate chemosensitizing nanoparticles (NPs) for tumor-targeted drug delivery. IDM was conjugated to a CSO backbone via amide bond formation, of which successful synthesis was confirmed by proton-nuclear magnetic resonance analyses. Doxorubicin (DOX)-loaded CI (CI10/DOX; CI:DOX=10:1 [w/w]) NPs with <75nm of mean diameter, polydispersity index of ∼0.2, and positive zeta potential were prepared. The release of DOX from the NPs was enhanced at acidic pH (pH 5.5 and 6.8) compared to physiological pH (pH 7.4). The release of IDM increased in the presence of A549 cell lysates. In A549 cells (human lung carcinoma cells), more efficient cellular uptake of CI10/DOX NPs than that of free DOX was observed by using confocal laser scanning microscopy and flow cytometry. The in vitro cytotoxicity of CI10/DOX NPs in A549 cells was higher than those of free DOX and CI NPs with free DOX groups. In vivo pharmacokinetic studies after intravenous administration in rats showed significantly lower clearance of DOX from NPs compared with the free DOX group. Tumor targetability of the developed CI NPs was also verified by a real-time optical imaging study. In summary, the chemosensitizing CI/DOX NP with enhanced anticancer activity, prolonged blood circulation, and passive tumor targeting can be a promising anticancer drug delivery system for tumor-targeted therapy. STATEMENT OF SIGNIFICANCE: Chemosensitizing nanoparticles (NPs) based on amphiphilic chitosan oligosaccharide-indomethacin (CSO-IDM; CI) conjugate were developed for tumor-targeted delivery of doxorubicin (DOX). IDM was introduced to the CSO backbone as a hydrophobic residue to synthesize an amphiphilic conjugate and a chemosenstizer of DOX for improving antitumor efficacies. IDM, conjugated to CSO, may inhibit the efflux of cellular uptaken DOX via multidrug resistance-associated protein (MRP) and subsequently augment the anti-proliferation potentials of DOX in A549 cells (MRP-expressed human lung cancer cells). Chemosensitizing properties of developed CI NPs were assessed in cell culture models and the tumor targetability of CI/DOX NPs was demonstrated in A549 tumor-xenografted mouse model by a real-time optical imaging. Developed CI NPs can be used as a multifunctional nanosystem for the therapy of MRP-expressed cancers.

Determination and validation of psammaplin A and its derivatives in rat plasma by liquid chromatography-tandem mass spectrometry and its application in pharmacokinetic study.

A liquid chromatography-tandem mass (LC-MS/MS) method was developed for the determination of psammaplin A (PsA) and its newly synthesized derivatives (PsA 107, PsA 109, and PsA 123) in rat plasma using bupropion as an internal standard (IS). The plasma samples were deproteinized with acetonitrile. Chromatographic separation was performed on hydro-RP column (75×2.0mm, 80Å, 4µm) with isocratic elution using 5mM ammonium formate buffer/acetonitrile (30:70, v/v) at a flow rate of 0.4mL/min and the total run time was 5min. Mass spectrometric detection was performed with positive electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode. The ion transitions monitored were m/z 663.2→331.0, 687.2→343.1, 587.3→293.1, 563.3→281.0, and 240.0→184.0 for PsA, PsA 107, PsA 109, PsA 123, and IS, respectively. All analytes showed good linearity over the concentration range of 5.00-5000ng/mL (r(2)≥0.994). The lower limit of quantification was 5ng/mL for PsA and its three PsA derivatives. Within- and between-run precisions (relative standard deviation, RSD) were less than 9.66% and accuracy (relative error, RE) ranged from -9.34% to 7.25%. Established method was successfully applied to the investigation of pharmacokinetic properties of PsA and its derivatives in rats after intravenous administration at a dose of 2mg/kg.