Aims
The aim of this meta‐analysis is to examine the impact of in‐hospital pharmacist‐led medication reviews in paediatric and adult patients.
Methods
Relevant studies were identified from the ...Medline and Cochrane Library databases. Studies were included if they met the following criteria (without any language or date restrictions): design: randomized controlled trial; intervention: in‐hospital pharmacist‐led medication review (experimental group) vs. usual care (control group); participants: paediatric or adult population. The primary outcome was all‐cause readmissions and/or emergency department (ED) visits at different time points. The secondary outcomes were all‐cause readmissions, all‐cause ED visits, drug‐related readmissions, mortality, length of hospital stay, adherence and quality of life. We calculated the relative risk (RR) or mean differences (MD) with 95% confidence intervals (CIs) for each study. We used fixed and/or random effects models. Heterogeneity was assessed using the I2 statistic.
Results
We systematically reviewed 19 randomized controlled trials (4805 participants). The readmission rates did not differ between the experimental group and the control group (RR = 0.97, 95% CI 0.89; 1.05, p = 0.470). The secondary outcomes did not differ between the two groups, except for in drug‐related readmissions, which were lower in the experimental group (RR = 0.25, 95% CI 0.14; 0.45, p < 0.001), and all‐cause ED visits (RR = 0.70, 95% CI 0.59; 0.85 p = 0.001).
Conclusion
The low‐quality evidence in this analysis suggests an impact of pharmacist‐led medication reviews on drug‐related readmissions and all‐cause ED visits. Few studies reported on adherence and quality of life. More high‐quality randomized clinical trials are needed to assess the impact of pharmacist‐led medication reviews on patient‐relevant outcomes, including adherence and quality of life.
Capable of generating plasmonic and other effects, gold nanostructures can offer a variety of diagnostic and therapy functionalities for biomedical applications, but conventional ...chemically-synthesized Au nanomaterials cannot always match stringent requirements for toxicity levels and surface conditioning. Laser-synthesized Au nanoparticles (AuNP) present a viable alternative to chemical counterparts and can offer exceptional purity (no trace of contaminants) and unusual surface chemistry making possible direct conjugation with biocompatible polymers (dextran, polyethylene glycol). This work presents the first pharmacokinetics, biodistribution and safety study of laser-ablated dextran-coated AuNP (AuNPd) under intravenous administration in small animal model. Our data show that AuNPd are rapidly eliminated from the blood circulation and accumulated preferentially in liver and spleen, without inducing liver or kidney toxicity, as confirmed by the plasmatic ALAT and ASAT activities, and creatininemia values. Despite certain residual accumulation in tissues, we did not detect any sign of histological damage or inflammation in tissues, while IL-6 level confirmed the absence of any chronic inflammation. The safety of AuNPd was confirmed by healthy behavior of animals and the absence of acute and chronic toxicities in liver, spleen and kidneys. Our results demonstrate that laser-synthesized AuNP are safe for biological systems, which promises their successful biomedical applications.
Self‐assembly of a covalently‐bound lipophilic drug to a dendronic scaffold for making organic nanoparticles is reported as a proof of concept in nanovectorization. A minimalist structural approach ...with a small PEG‐dendron conjugated to paclitaxel (PTX), incorporating safe succinic and gallic acids, is efficient to provide the expected anticancer bioactivity, but also significantly retards and targets intracellular delivery of PTX in 2D and 3D lung cancer cell cultures. A branching effect of dendrons is crucial, when compared to linear PTX conjugates. Transmission electron microscopy (TEM) and dynamic light‐scattering (DLS) studies indicate the formation of stable, low‐disperse nanoparticles at 10−5 m in H20, which could also be responsible for the biological effects. An ultrasensitive LC‐MS/MS method was used for the determination of intracellular PTX concentration over time, along with the survival rates of cancer cells. Similarly, cell survival assays were successfully correlated to a 3D cell culture with spheroids for mimicking tumors, when treated with PTX conjugates. Our work opens the way to a full evaluation program required for new chemical entities.
Self‐assembly of a covalently‐bound lipophilic drug to a dendron for making organic nanoparticles is reported as a minimalist concept in nanovectorization. A small dendron conjugated to paclitaxel (PTX) provide nanoparticles and branching effects. It significantly retards intracellular delivery of PTX in 2D and 3D cell cultures. TEM/DLS studies are conclusive for monodisperse NPs. Intracellular PTX was measured by LC‐MS/MS. PTX conjugates were efficient in 3D cell cultures which mimic tumors. It provides a better mean to evaluate the in vitro efficacy of PTX‐conjugates to kill tumors.
Exhibiting a red-shifted absorption/scattering feature compared to conventional plasmonic metals, titanium nitride nanoparticles (TiN NPs) look as very promising candidates for biomedical ...applications, but these applications are still underexplored despite the presence of extensive data for conventional plasmonic counterparts. Here, we report the fabrication of ultrapure, size-tunable TiN NPs by methods of femtosecond laser ablation in liquids and their biological testing. We show that TiN NPs demonstrate strong and broad plasmonic peak around 640-700 nm with a significant tail over 800 nm even for small NPs sizes (<7 nm). In vitro tests of laser-synthesized TiN NPs on cellular models evidence their low cytotoxicity and excellent cell uptake. We finally demonstrate a strong photothermal therapy effect on U87-MG cancer cell cultures using TiN NPs as sensitizers of local hyperthermia under near-infrared laser excitation. Based on absorption band in the region of relative tissue transparency and acceptable biocompatibility, laser-synthesized TiN NPs promise the advancement of biomedical modalities employing plasmonic effects, including absorption/scattering contrast imaging, photothermal therapy, photoacoustic imaging and SERS.
Glioblastoma (GBM) is a very aggressive primary malignant brain tumor and finding effective therapies is a pharmaceutical challenge and an unmet medical need. Photothermal therapy may be a promising ...strategy for the treatment of GBM, as it allows the destruction of the tumor using heat as a non-chemical treatment for disease bypassing the GBM heterogeneity limitations, conventional drug resistance mechanisms and side effects on peripheral healthy tissues. However, its development is hampered by the distinctive features of this tumor. Photoabsorbing agents such as nanoparticles need to reach the tumor site at therapeutic concentrations, crossing the blood-brain barrier upon systemic administration. Subsequently, a near infrared light irradiating the head must cross multiple barriers to reach the tumor site without causing any local damage. Its power intensity needs to be within the safety limit and its penetration depth should be sufficient to induce deep and localized hyperthermia and achieve tumor destruction. To properly monitor the therapy, imaging techniques that can accurately measure the increase in temperature within the brain must be used. In this review, we report and discuss recent advances in nanoparticle-mediated plasmonic photothermal therapy for GBM treatment and discuss the preclinical challenges commonly faced by researchers to develop and test such systems.
The therapeutic management of gliomas remains particularly challenging. Brain tumors present multiple obstacles that make therapeutic innovation complex, mainly due to the presence of blood-tumor and ...blood-brain barriers (BTB and BBB, respectively) which prevent penetration of anticancer agents into the brain parenchyma. Focused ultrasound-mediated BBB disruption (FUS-BBBD) provides a physical method for non-invasive, local, and reversible BBB disruption. The safety of this technique has been demonstrated in small and large animal models. This approach promises to enhance drug delivery into the brain tumor and therefore to improve survival outcomes by repurposing existing drugs. Several clinical trials continue to be initiated in the last decade. In this review, we provide an overview of the rationale behind the use of FUS-BBBD in gliomas and summarize the preclinical studies investigating different approaches (free drugs, drug-loaded microbubbles and drug-loaded nanocarriers) in combination with this technology in in vivo glioma models. Furthermore, we discuss the current state of clinical trials and devices developed and review the challenges to overcome for clinical use of FUS-BBBD in glioma therapy.
Due to excellent biocompatibility, chemical stability, and promising optical properties, gold nanoparticles (Au-NPs) are the focus of research and applications in nanomedicine. Au-NPs prepared by ...laser ablation in aqueous biocompatible solutions present an essentially novel object that is unique in avoiding any residual toxic contaminant. This paper is conceived as the next step in development of laser-ablated Au-NPs for future in vivo applications. The aim of the study was to assess the safety, uptake, and biological behavior of laser-synthesized Au-NPs prepared in water or polymer solutions in human cell lines. Our results showed that laser ablation allows the obtaining of stable and monodisperse Au-NPs in water, polyethylene glycol, and dextran solutions. The three types of Au-NPs were internalized in human cell lines, as shown by transmission electron microscopy. Biocompatibility and safety of Au-NPs were demonstrated by analyzing cell survival and cell morphology. Furthermore, incubation of the three Au-NPs in serum-containing culture medium modified their physicochemical characteristics, such as the size and the charge. The composition of the protein corona adsorbed on Au-NPs was investigated by mass spectrometry. Regarding composition of complement C3 proteins and apolipoproteins, Au-NPs prepared in dextran solution appeared as a promising drug carrier. Altogether, our results revealed the safety of laser-ablated Au-NPs in human cell lines and support their use for theranostic applications.
The quinoxaline core is a promising scaffold in medicinal chemistry. Multiple quinoxaline derivatives, such as the topoisomerase IIβ inhibitor XK-469 and the tissue transglutaminase 2 inhibitor ...GK-13, have been evaluated for their antiproliferative activity. Previous work reported that quinoxaline derivatives bearing an oxirane ring present antiproliferative properties against neuroblastoma cell lines SK-N-SH and IMR-32. Likewise, quinoxalines with an arylethynyl group displayed promising antineoplastic properties against glioblastoma and lung cancer cell lines, U87-MG and A549 respectively. Here, 40 new quinoxaline derivatives bearing an oxirane ring were synthesized using a tetrakis(dimethylamino)ethylene (TDAE) strategy and a Sonogashira cross-coupling reaction. Each reaction with TDAE furnished a pair of diastereoisomers cis and trans. These new compounds formed two series according to the substitution of position 2 on the quinoxaline core, with chlorine or phenylacetylene respectively. Each of these isomers was evaluated for antiproliferative activity against neuroblastoma cell lines SK-N-SH and IMR-32 by MTT assay. All cell viability assay results were analyzed using R programming, as well as a statistical comparison between groups of compounds. Our evaluation showed no difference in drug sensitivity between the two neuroblastoma cell lines. Moreover, trans derivatives were observed to display better activities than cis derivatives, leading us to conclude that stereochemistry plays an important role in the antiproliferative activity of these compounds. Further support for this hypothesis is provided by the lack of improvement in antineoplastic activity following the addition of the phenylacetylene moiety, probably due to steric hindrance. As a result, compounds with nitrofuran substituents from the TDAE series demonstrated the highest antiproliferative activity with IC50 = 2.49 ± 1.33 μM and IC50 = 3.96 ± 2.03 μM for compound 11a and IC50 = 5.3 ± 2.12 μM and IC50 = 7.12 ± 1.59 μM for compound 11b against SK-N-SH and IMR-32, respectively. Furthermore, an in silico study was carried out to evaluate the mechanism of action of our lead compounds and predict their pharmacokinetic properties.
Si/SiOx nanoparticles (NPs) produced by laser ablation in deionized water or aqueous biocompatible solutions present a novel extremely promising object for biomedical applications, but the ...interaction of these NPs with biological systems has not yet been systematically examined. Here, we present the first comprehensive study of biodistribution, biodegradability and toxicity of laser-synthesized Si-SiOx nanoparticles using a small animal model. Despite a relatively high dose of Si-NPs (20 mg/kg) administered intravenously in mice, all controlled parameters (serum, enzymatic, histological etc.) were found to be within safe limits 3 h, 24 h, 48 h and 7 days after the administration. We also determined that the nanoparticles are rapidly sequestered by the liver and spleen, then further biodegraded and directly eliminated in urine without any toxicity effects. Finally, we found that intracellular accumulation of Si-NPs does not induce any oxidative stress damage. Our results evidence a huge potential in using these safe and biodegradable NPs in biomedical applications, in particular as vectors, contrast agents and sensitizers in cancer therapy and diagnostics (theranostics).
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