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This study aimed to enhance the efficacy of quercetin (QT) by formulating it into a liposomal drug delivery system utilizing the concept of central composite design. The drug:lipid ratio, cholesterol concentration, and sonication time were selected as independent variables in the study. The vesicle and percentage entrapment efficiency were selected as the dependent variables. Quercetin nanoliposomes (QT-NLs) were prepared via a combination of ethanol injection and thin film hydration. The vesicle size and entrapment efficiency of all formulations were within the ranges of 100 nm and >80 %, respectively. The zeta potential value indicated the stability of the optimized formulation. The contour plots were used to select the desired batch range. SEM studies revealed an imperfect crystalline morphology without any unwanted agglomeration. MTT assays on VERO cell lines indicated the safety of the developed formulation. MTT assays of MCF-7 cells revealed IC50 values of 5.8 μM and 7.9 μM for QT-NLs and QT, respectively. In our study, the optimized formulation exhibited late and early apoptosis and necrosis when used to treat MCF-7 cells. S and G2/M cell cycle phases of MCF-7 cell arrest were confirmed by the cell cycle report. At sub-G0/G1 phase, 2.10 ± 1.1 %; G0/G1 phase, 34.13 ± 1.9 %; S phase, 34.55 ± 0.98 %; and G2/M phase, 26.24 ± 1.7 % of cell arrest were observed. The results demonstrated the effectiveness of the proposed design for the development of corn starch-coated QT-NLs and their activity in breast cancer cell lines.

Abstract Background Today, artificial intelligence-based computational approach is facilitating multitasking and interdisciplinary analytical research. For example, the data gathered during an analytical research project such as spectral and chromatographic data can be used in predictive experimental research. The spectral and chromatographic information plays crucial role in pharmaceutical research, especially use of instrumental analytical approaches and it consume time, man power, and money. Hence, predictive analysis would be beneficial especially in resource-limited settings. Main body Computational approaches verify data at an early phase of study in research process. Several in silico techniques for predicting analyte’s spectral and chromatographic characteristics have recently been developed. Understanding of these tools may help researchers to accelerate their research with boosted confidence and prevent researchers from being misled by incorrect analytical data. In this communication, the properties of chemical compounds and its relation to chromatographic retention will be discussed, as well as the prediction technique for UV/IR/Raman/NMR spectrograms. This review looked at the reference data of chemical compounds to compare the predictive ability in silico tools along with the percentage error, limitations, and advantages. Conclusion The computational prediction of analytical characteristics offers a wide range of applications in academic research, bioanalytical method development, computational chemistry, analytical method development, data analysis approaches, material characterization, and validation process.

Abstract We evaluated the anti-leishmanial efficacy of different saturated medium-chain fatty acids (FAs, C8–C18) where FA containing C8 chain, caprylic acid (CA), was found to be most potent against Leishmania donovani, the causative agent for visceral leishmaniasis (VL). Different analogs of CA with C8 linear chain, but not higher, along with a carboxyl/ester group showed a similar anti-leishmanial effect. Ergosterol depletion was the major cause of CA-mediated cell death. Molecular docking and molecular dynamic simulation studies indicated the enzyme mevalonate kinase (MevK) of the ergosterol biosynthesis pathway as a possible target of CA. Enzyme assays with purified recombinant MevK and CA/CA analogs confirmed the target with a competitive inhibition pattern. Using biochemical and biophysical studies; strong binding interaction between MevK and CA/CA analogs was established. Further, using parasites with overexpressed MevK and proteomics studies of CA-treated parasites the direct role of MevK as the target was validated. We established the mechanism of the antileishmanial effect of CA, a natural product, against VL where toxicity and drug resistance with current chemotherapeutics demand an alternative. This is the first report on the identification of an enzymatic target with kinetic parameters and mechanistic insights against any organism for a natural medium-chain FA.

Abstract Background The present study was aimed to enhance the solubility and dissolution of BCS class II drug, telmisartan (TEM), by nanoformulation approach. Several attempts were made to develop a nanosuspension by bottom-up and top-down techniques. In our study, we found in situ nanoamorphization technique to be incompatible and hence was not selected for further development of nanoformulation. Bottom-up techniques such as anti-solvent precipitation and emulsification solvent evaporation methods failed to reduce the size of the drug to nanoform by HPMC E15 and PVP K-25 at 1500–2000 rpm but resulted in micron-sized particles. Results However, the acid-base neutralization method has produced nanosuspension with a particle size of 243.9 nm and 0.119 PDI. Formulation and analytical development were carried out by statistical factorial design using the Design-Expert software (version 11.0). The nanosuspensions remained stable even after 90 days without any aggregations with particle size 338.1 nm and PDI 0.146. Zeta potential of optimized formulation was found to be − 16.2 mV. Drug content and its release were estimated by the developed and validated in-house HPLC method. In vitro drug diffusion studies on the optimized formulation have shown a drug release of 82.6% by the end of 3 h, whereas plain drug suspension has shown only 42.8% release, indicating a 2-fold increase of drug diffusion with nanosuspension. Ex vivo drug permeation studies performed using excised goat gastric mucosa revealed much faster permeation of TEM from nanosuspension than the plain drug suspension. Conclusions Hence, from the results, it can be concluded that TEM, when formulated by acid-base neutralization method as a nanosuspension, leads to enhanced solubility, dissolution, and stability.

PurposeThe Accessible Cancer Care to Enable Support for Cancer Survivors (ACCESS) program adopts a multidisciplinary supportive care model with routine distress screening to triage newly diagnosed cancer survivors for additional support on the basis of distress levels. This study aimed to evaluate the clinical impact of ACCESS over 1 year.MethodsWe performed cluster random assignment at the oncologist level in a 1:1 ratio to receive ACCESS or usual care. Participants 21 years and older, newly diagnosed with breast or gynecologic cancer, and receiving care at National Cancer Centre Singapore were included. Outcomes assessed every 3 months for 1 year included quality of life (QoL) (primary), functioning, physical and psychological symptom burden, and activity levels. Data were analyzed using mixed-effects models.ResultsParticipants from 16 clusters (control = 90, intervention = 83) were analyzed. The ACCESS program did not significantly improve QoL (primary outcome). However, compared with usual care recipients, ACCESS recipients reported higher physical functioning (P = .017), role functioning (P = .001), and activity levels (P < .001) at 9 months and lower psychological distress (P = .025) at 12 months. ACCESS recipients screened with high distress had poorer QoL, lower role and social functioning, and higher physical symptom distress at 3 months but had comparable scores with ACCESS recipients without high distress after 12 months.ConclusionCompared with usual care, participation in the ACCESS program did not yield QoL improvement but showed earlier functioning recovery related to activities of daily living and reduced psychological distress. Routine distress screening is a promising mechanism to identify survivors with poorer health for more intensive supportive care.

ABSTRACT: The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell‐based immune therapies including chimeric antigen receptor T lymphocyte (CAR‐T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune‐related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune‐related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI‐related myocarditis with cardiogenic shock to more common complications including less severe ICI‐related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non‐inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR‐T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus.

Although the 2021 Western North America (WNA) heat wave was predicted by weather forecast models, questions remain about whether such strong events can be simulated by global climate models (GCMs) at different model resolutions. Here, we analyze sets of GCM simulations including historical and future periods to check for the occurrence of similar events. High- and low-resolution simulations both encounter challenges in reproducing events as extreme as the observed one, particularly under the present climate. Relatively stronger amplitudes are observed during the future periods. Furthermore, high- and low-resolution short initialized GCM simulations are both able to reasonably predict such strong events and their associated high-pressure ridge over the WNA with a 1 week forecast lead time. Moisture sensitivity experiments further indicate a drier atmospheric moisture condition results in substantially higher near-surface temperatures in the simulated heat events.