Article
Chemistry, Multidisciplinary
Tao Wang, Liang Sun, Tianyu Ren, Min Hou, Ying Long, Jian-Hui Jiang, Jianjun He
Summary: Protein-degrading chimeras, such as lysosome-targeting exosomes (LYTEXs), are effective drug modalities for treating diseases caused by abnormal protein expression. LYTEXs, genetically engineered exosomes expressing multivalent single-chain fragment variables, can selectively degrade membrane protein targets, providing a generalizable and easy-to-prepare platform for modulating surface protein expression.
Article
Cell Biology
Chunyan Yang, Zixuan Guan, Xincheng Pang, Zengqi Tan, Xiaomin Yang, Xiang Li, Feng Guan
Summary: A delivery system based on mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) loaded with doxorubicin (Dox) was developed for potential therapy of hepatocellular carcinoma (HCC). The desialylated MSC-EVs exhibited improved cellular uptake and targeting efficacy in vitro and in vivo.
Article
Chemistry, Multidisciplinary
Jia Nong, Patrick M. M. Glassman, Jacob W. W. Myerson, Viviana Zuluaga-Ramirez, Alba Rodriguez-Garcia, Alvin Mukalel, Serena Omo-Lamai, Landis R. R. Walsh, Marco E. E. Zamora, Xijing Gong, Zhicheng Wang, Kartik Bhamidipati, Raisa Y. Y. Kiseleva, Carlos H. H. Villa, Colin Fred Greineder, Scott E. E. Kasner, Drew Weissman, Michael J. J. Mitchell, Silvia Muro, Yuri Persidsky, Jacob Samuel Brenner, Vladimir R. R. Muzykantov, Oscar A. A. Marcos-Contreras
Summary: The study investigated the loading of nanoparticles targeted to intercellular adhesion molecule 1 (anti-ICAM/NP) into white blood cells (WBC) in vivo, bypassing the ex vivo manipulation. The results showed successful transport of anti-ICAM/NP to pathological foci in the central nervous system (CNS) through the migration of WBCs from the lungs. This method could be clinically significant in the treatment of acute brain inflammation and reduction of brain edema.
Article
Chemistry, Medicinal
Ahmed M. Fatouh, Ahmed H. Elshafeey, Ahmed Abdelbary
Summary: The study successfully enhanced the delivery of ledipasvir to hepatocytes and prolonged its retention within the liver by synthesizing galactosylated chitosan and coating it on liposomes. The coated liposomes exhibited a small particle size, high entrapment efficiency, and significantly improved uptake of ledipasvir into targeted hepatocytes. Pharmacokinetic analysis revealed increased liver concentration and prolonged half-life and residence time compared to oral dispersal of ledipasvir.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Francesca Perrone, Emanuela Fabiola Craparo, Maja Cemazar, Urska Kamensek, Salvatore Emanuele Drago, Barbara Dapas, Bruna Scaggiante, Fabrizio Zanconati, Debora Bonazza, Mario Grassi, Nhung Truong, Gabriele Pozzato, Rossella Farra, Gennara Cavallaro, Gabriele Grassi
Summary: The study demonstrates the valuable potential of PDPG for specific delivery of siRNAs targeting HCC-related genes, leading to reduced HCC cell vitality and downregulation of target gene expression.
JOURNAL OF CONTROLLED RELEASE
(2021)
Review
Pharmacology & Pharmacy
Jia Nong, Patrick M. Glassman, Vladimir R. Muzykantov
Summary: Acute inflammation is a common component of many prevalent conditions, and targeting endothelial cells for therapeutic intervention shows promise in correcting the damaging effects of inflammation. However, current drugs and drug delivery systems lack precision and effectiveness.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Review
Pharmacology & Pharmacy
Biagio Todaro, Elisa Ottalagana, Stefano Luin, Melissa Santi
Summary: Peptides, similar to oligonucleotide aptamers and antibodies, can be used as targeting molecules. They have high production efficiency and stability in physiological environments. In recent years, they have been extensively studied for targeting various diseases, including tumors and central nervous system disorders, due to their ability to cross the blood-brain barrier. This review discusses the techniques for designing peptides experimentally and in silico, as well as their potential applications. It also explores advancements in their formulation and chemical modifications to enhance their stability and effectiveness. Furthermore, the review explores how peptides could be effectively utilized to overcome physiological challenges and improve existing treatments.
Article
Chemistry, Multidisciplinary
Selvi Srinivasan, Debashish Roy, Thomas E. J. Chavas, Vladimir Vlaskin, Duy-Khiet Ho, Ayumi Pottenger, Clare L. M. LeGuyader, Mahdi Maktabi, Pamela Strauch, Conner Jackson, Siobhan M. Flaherty, Hsiuling Lin, Jing Zhang, Brandon Pybus, Qigui Li, Hans E. Huber, Paul A. Burke, David Wesche, Rosemary Rochford, Patrick S. Stayton
Summary: Primaquine and tafenoquine are two 8-aminoquinoline antimalarial drugs approved for malarial radical cure, but they cause hemolytic anemia in G6PD-deficient individuals. By synthesizing these drugs as liver-targeted prodrugs, liver exposure can be maximized, erythrocyte exposure minimized, toxicity reduced, and efficacy improved. Liver-targeted tafenoquine polymers have shown promising results in preclinical studies, with potential for single-dose therapeutic use without the need for G6PD diagnosis.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Biochemistry & Molecular Biology
Igor D. Zlotnikov, Maksim A. Vigovskiy, Maria P. Davydova, Milan R. Danilov, Uliana D. Dyachkova, Olga A. Grigorieva, Elena V. Kudryashova
Summary: This study synthesized mannosylated carriers for targeted drug delivery to macrophages. The carriers showed potential for creating various medicinal forms, and exhibited non-specific capture of cells and increased selectivity to CD206+ macrophages.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Nanoscience & Nanotechnology
Yezi Chen, Xiaoqin Luo, Yun Liu, Yunlei Zou, Shiqi Yang, Chaoqi Liu, Yun Zhao
Summary: Ultrasound nanobubbles were prepared as drug carriers for targeted delivery of programmed death ligand 1 monoclonal antibody (PD-L1 mAb) and doxorubicin (DOX). The nanobubbles showed significant synergistic antitumor effects by combining immunotherapy and chemotherapy, providing a potential strategy for hepatocellular carcinoma (HCC) treatment.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2022)
Article
Chemistry, Multidisciplinary
Yi Du, Qiwei Wang, Lili Shi, Tao Li
Summary: DNA-assembled multiaptamer systems offer a promising approach for targeted delivery of nucleic acid cargoes. In this study, a G-quadruplex-proximized aptamer system was engineered for efficient transmembrane delivery of siRNA, showing great potential for precise anticancer therapy.
Article
Pharmacology & Pharmacy
Andrew R. Willmer, Steven Dunne, Rosemary Swanson, Deepak Almeida, Nicole C. Ammerman, Kathleen A. Stringer, Edmund V. Capparelli, Gus R. Rosania
Summary: This passage describes a pharmacokinetic modeling study of Clofazimine (CFZ). By analyzing the data from CFZ-treated mice, it was found that using an adaptive Vd model could provide a more accurate fit of the drug concentrations. Additionally, incorporating a nonlinear sigmoidal equation into the model can better capture the phase transition of drug disposition.
Article
Chemistry, Multidisciplinary
Rabia Arshad, Tanveer A. Tabish, Maria Hassan Kiani, Ibrahim M. Ibrahim, Gul Shahnaz, Abbas Rahdar, Misook Kang, Sadanand Pandey
Summary: The hyaluronic acid-functionalized self-nano emulsifying drug delivery system (HA-CIP-SNEDDS) effectively improved the biopharmaceutical parameters of CIP, demonstrating enhanced permeation ability through goat intestinal mucus. Compared to free CIP, HA-CIP-SNEDDS exhibited stronger anti-biofilm activity, improved biocompatibility, and enhanced oral pharmacokinetics.
Article
Pharmacology & Pharmacy
Mohsen Rezaeian, M. Soltani, Ahmad Naseri Karimvand, Kaamran Raahemifar
Summary: Intraperitoneal chemotherapy has limitations in delivering drugs to peritoneal malignancies. This study developed a mathematical model to investigate the efficacy of magnetically controlled drug targeting (MCDT) in intraperitoneal chemotherapy. The results showed that MCDT improved drug penetration depth and area, as well as increased the fraction of killed cells in the tumor compared to conventional IP chemotherapy. The study also evaluated the effects of magnetic strength, magnet-tumor distance, and nanoparticle size on MCDT efficacy.
Article
Biochemistry & Molecular Biology
Zeyad AlMajed, Najla M. Salkho, Hana Sulieman, Ghaleb A. Husseini
Summary: This study performed comprehensive model fitting for liposomal release profiles triggered by ultrasound. Different frequencies and power densities of ultrasound were tested, and various models were evaluated for their fitting performance. The results showed that different models fit well to the release profiles under different conditions. These models can aid in predicting drug release in future in vitro studies.
Article
Veterinary Sciences
Elodie Anne Lallemand, Claudine Zemirline, Pierre-Louis Toutain, Alain Bousquet-Melou, Aude A. Ferran, Severine Boullier
Summary: This study demonstrates that macrophages can cooperate with cephalexin at lower bacterial inoculum sizes and protect Staphylococcus aureus from cephalexin killing activity, but are overwhelmed when exposed to large inoculums. Increasing the bacterial inoculum size results in decreased macrophage viability and reduced bactericidal activity, with the highest inoculum size leading to higher bacterial counts in the presence of macrophages and cephalexin compared to cephalexin alone.
BMC VETERINARY RESEARCH
(2021)
Article
Veterinary Sciences
Taisuke Kuroda, Yohei Minamijima, Hidekazu Niwa, Norihisa Tamura, Hiroshi Mita, Kentaro Fukuda, Masahiro Kaimachi, Yuto Suzuki, Yuki Enoki, Kazuaki Taguchi, Kazuaki Matsumoto, Pierre-Louis Toutain, Alain Bousquet-Melou, Yoshinori Kasashima
Summary: The study found that different dosage regimens of first-generation cephalosporins cephalothin and cefazolin are required to control infections in horses based on the MIC90 against different bacteria, according to PK/PD concepts.
EQUINE VETERINARY JOURNAL
(2021)
Article
Veterinary Sciences
Alain Bousquet-Melou, Marc Schneider, Farid El Garch, Diane C. Broussou, Aude A. Ferran, Elodie A. Lallemand, Cyrielle Triboulloy, Peter Damborg, Pierre-Louis Toutain
Summary: The study calculated PK/PD cut-offs for Marbofloxacin in horses to determine susceptibility to Gram-positive and Gram-negative pathogens based on pharmacokinetic data. However, the main limitation is the lack of inclusion of clinical data in establishing these cut-offs.
EQUINE VETERINARY JOURNAL
(2021)
Article
Multidisciplinary Sciences
JingJing Liu, Jean-Yves Madec, Alain Bousquet-Melou, Marisa Haenni, Aude A. Ferran
Summary: Non-antibiotic substances subtilisin A and calcium gluconate were found to significantly reduce the biomass of S. aureus biofilms, while antibiotics alone had limited effects. Combining antibiotics with calcium gluconate or subtilisin A led to an additive reduction of embedded biofilm bacteria in susceptible isolates. Further studies are needed to understand factors contributing to susceptibility to these combinations in specific isolates.
SCIENTIFIC REPORTS
(2021)
Article
Pharmacology & Pharmacy
Alain Bousquet-Melou, Anne Lespine, Jean-Francois Sutra, Isabelle Bargues, Pierre-Louis Toutain
Summary: Research on an obese dog model suggests that in obese subjects, the maintenance doses of Ivermectin (IVM) and moxidectin (MOX) should be based on lean body weight, while loading doses should be based on total body weight.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Infectious Diseases
Carmen Espinosa-Gongora, Lisbeth Rem Jessen, Oliver James Dyar, Alain Bousquet-Melou, Bruno Gonzalez-Zorn, Celine Pulcini, Giovanni Re, Stefan Schwarz, Dorina Timofte, Pierre-Louis Toutain, Luca Guardabassi
Summary: The study revealed discrepancies in antimicrobial stewardship education among European veterinary students, with only one in four students familiar with guidelines for antimicrobial use. 75% of students felt the need for improved teaching, with half of them requesting more education on general antimicrobial therapy.
Article
Microbiology
Veronique Dupouy, Jean-Yves Madec, Jessica Wucher, Nathalie Arpaillange, Veronique Metayer, Beatrice Roques, Alain Bousquet-Melou, Marisa Haenni
Summary: This study highlighted the importance of both cefquinome exposure and initial ESBL colonization level in the ESBL selection and amplification process in calves' guts. It also demonstrated the dose-independent effect of cefquinome administration on the selection and amplification of ESBL-producing E. coli. The recovery of the blaCTX-M-1/IncI1 ST3 plasmid after cefquinome exposure suggests its epidemic success in this context.
VETERINARY MICROBIOLOGY
(2021)
Article
Microbiology
Quentin Valle, Beatrice B. Roques, Alain Bousquet-Melou, David Dahlhaus, Felipe Ramon-Portugal, Veronique Dupouy, Delphine Bibbal, Aude A. Ferran
Summary: Minocycline shows potential activity against multidrug-resistant bacteria, but may impact gut microbiota during treatment. Research found that minocycline concentrations in the intestines were higher than in plasma, but its activity in large intestine content was lower than in a standard broth.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Medicinal
Sandrine Kappler-Gratias, Leo Bucher, Sokunthea Top, Charlotte Quentin-Froignant, Nicolas Desbois, Stephane Bertagnoli, Matthieu Louison, Emma Monge, Alain Bousquet-Melou, Marlene Lacroix, Claude P. Gros, Franck Gallardo
Summary: Experimental results demonstrate that a corrole compound shows the most promising antiviral effects against the myxoma virus, displaying high selectivity and low IC50, with easy synthesis. Furthermore, the compound exhibits no significant toxicity, and in vivo tests indicate that it can alleviate symptoms and promote weight gain in infected animals.
ACS INFECTIOUS DISEASES
(2021)
Article
Environmental Sciences
Mailie Saint-Hilaire, Aurore Fourcot, Alain Bousquet-Melou, Guido Rychen, Jean-Pierre Thome, Julien Parinet, Cyril Feidt, Agnes Fournier
Summary: The study found that the major route of excretion for chlordecone in contaminated ewes is through feces, accounting for 86% of the administered dose, with 51% as chlordecone and 35% as chlordecol.
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
(2021)
Article
Microbiology
Aurore Perault, Catherine Turlan, Nathalie Eynard, Quentin Valle, Alain Bousquet-Melou, Etienne Giraud
Summary: Recent studies have shown that both resistance and tolerance/persistence levels can evolve rapidly in bacteria exposed to repeated antibiotic treatments. This study used in vitro evolution to explore the selection of tolerant/hyperpersistent Escherichia coli mutants under repeated exposure to high ciprofloxacin concentration. The researchers found that mutants with hyperpersistence specific to fluoroquinolones emerged, without a significant increase in minimum inhibitory concentration. This research highlights the importance of considering tolerance/persistence phenotypes in addition to resistance in antibiotic therapy selection.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
Aude A. Ferran, Marlene Z. Lacroix, Ophelie Gourbeyre, Alicia Huesca, Baptiste Gaborieau, Laurent Debarbieux, Alain Bousquet-Melou
Summary: The development of antibiotic resistance in bacteria compromises the effectiveness of antibiotics and bacteriophages. This study demonstrates that combining phages with antibiotics can prevent the growth of resistant clones.
MICROBIOLOGY SPECTRUM
(2022)
Article
Pharmacology & Pharmacy
Felipe Ramon Portugal, Marlene Z. Lacroix, Beatrice B. Roques, Veronique Gayrard, Pierre-Louis Toutain, Alain Bousquet-Melou
Summary: Doxycycline, an antibiotic commonly used in pig farming, has been found to have a higher free fraction than previously estimated. The protein binding of doxycycline in pig plasma was measured using an equilibrium dialysis method and found to have a mean fu value of 31%. This new data has implications for the calculation of PK/PD cut-offs used in antimicrobial susceptibility testing.
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Pierre-Louis Toutain, Peggy Gandia, Ludovic Pelligand, Aude A. Ferran, Peter Lees, Alain Bousquet-Melou, Didier Concordet
Summary: The confusion between free concentration and unbound fraction in medical literature has led to biased computations, erroneous interpretations, and misleading recommendations. This paper highlights these problems in the context of calculating Probability of Target Attainment (PTA), which is used for interpreting Antimicrobial Susceptibility Testing. The use of total plasma concentrations scaled by the unbound fraction inevitably results in biased estimates, especially when the variability associated with the unbound fraction is added instead of removed.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Emmanuelle Totain, Loic Lindner, Nicolas Martin, Yolande Misseri, Alexandra Iche, Marie-Christine Birling, Tania Sorg, Yann Herault, Alain Bousquet-Melou, Pascale Bouille, Christine Duthoit, Guillaume Pavlovic, Severine Boullier
Summary: This study used C216 candidate therapeutic vaccine to validate its efficacy in mouse and dog models for HPV infections. Animal models with easily transposable genetic design were developed to evaluate candidate vaccines. Results showed that although C216 vaccine had strong immunogenicity, it did not induce a sufficiently strong immune response to eliminate infected cells.
LABORATORY ANIMAL RESEARCH
(2023)