Review
Pharmacology & Pharmacy
Anna Gliszczynska, Elena Sanchez-Lopez
Summary: The S-(+) enantiomer of ibuprofen, dexibuprofen (DXI), is more potent than its R-(-) form with lower toxicity, greater clinical efficacy, and lesser variability in therapeutic effects. Recent research suggests that DXI not only has anti-inflammatory properties but also potential in reducing cancer development and preventing neurodegenerative diseases. Novel formulations of DXI are being designed to enhance therapeutic benefits and minimize adverse effects.
Article
Chemistry, Medicinal
Chunlei Wu, Zhehong Cheng, Danyi Lu, Ke Liu, Yulian Cheng, Pengxin Wang, Yimin Zhou, Meiqing Li, Ximing Shao, Hongchang Li, Wu Su, Lijing Fang
Summary: Researchers discovered a simplified analogue of Coibamide A and designed two novel peptide-drug conjugates, with one showing better drug release in vitro and significant tumor growth suppression in mice-bearing human tumor xenografts, indicating great potential in cancer drug discovery.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
Jundong Zhu, Tao Guo, Zheng Wang, Yanjun Zhao
Summary: Azobenzene and its derivatives are multifunctional molecules that are sensitive to light, hypoxia, and specific enzymes, making them potentially useful in material science, pharmaceutical science, and biomedicine. This article focuses on their application in triggered prodrugs and drug delivery systems, and discusses relevant issues and potential solutions.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Chemistry, Multidisciplinary
Farrukh Vohidov, Jannik N. Andersen, Kyriakos D. Economides, Michail Shipitsin, Olga Burenkova, James C. Ackley, Bhavatarini Vangamudi, Hung V-T Nguyen, Nolan M. Gallagher, Peyton Shieh, Matthew R. Golder, Jenny Liu, William K. Dahlberg, Deborah J. C. Ehrlich, Julie Kim, Samantha L. Kristufek, Sung Jin Huh, Allison M. Neenan, Joelle Baddour, Sattanathan Paramasivan, Elisa de Stanchina, Gaurab Kc, David J. Turnquist, Jennifer K. Saucier-Sawyer, Paul W. Kopesky, Samantha W. Brady, Michael J. Jessel, Lawrence A. Reiter, Donald E. Chickering, Jeremiah A. Johnson, Peter Blume-Jensen
Summary: The study introduces a macromolecular prodrug platform for BET protein inhibitors, which demonstrates a correlation between in vitro prodrug activation kinetics and in vivo tumor pharmacokinetics. This platform allows for the predictive design of novel BET protein inhibitors with enhanced anticancer efficacies and reduced dose-limiting toxicities, potentially overcoming hurdles in drug development.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Yongfei Yin, Penghao Sun, Hongqiang Dong, Yi Chen, Shigui Chen, Lu Wang
Summary: This study constructs novel supramolecular nanoparticles (BODIPY-CPT-NPs) for chemo-photodynamic combination cancer therapy through orthogonal host-guest recognitions and co-assembly. The nanoparticles allow for easy and precise control of the ratio of prodrugs and photosensitizers and exhibit excellent stability and photobleaching resistance. The combined effects of the BODIPY-CPT-NPs have been verified in CT26 and HeLa cancer cells.
CHINESE CHEMICAL LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Tovi Shapira-Furman, Abraham J. Domb
Summary: This report introduces a novel approach of nano formulation using stereo-interaction mechanism with poly(D-lactide)-polyethylene glycol (D-PLA-PEG) to address the challenges of controlled drug delivery for peptide and protein therapeutics. The study demonstrates that nano particles formed by the interaction between water-soluble D-PLA-PEG and insulin can achieve sustained release of insulin, showing potential application in diabetes treatment.
MACROMOLECULAR BIOSCIENCE
(2023)
Article
Pharmacology & Pharmacy
Eleonore Coppens, Didier Desmaele, Timothee Naret, Sebastien Garcia-Argote, Sophie Feuillastre, Gregory Pieters, Catherine Cailleau, Jean-Louis Paul, Bastien Prost, Audrey Solgadi, Jean-Philippe Michel, Magali Noiray, Patrick Couvreur, Simona Mura
Summary: The study showed that inducing drug insertion into lipoproteins through chemical modification is a simple approach to achieve lipoprotein-mediated drug delivery. While the lipid moiety plays a key role in the interaction between the drug and lipoproteins, the overall physicochemical features of the nanoparticles must also be carefully considered.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Review
Pharmacology & Pharmacy
Jiajia Xiang, Xin Liu, Guiping Yuan, Runnan Zhang, Quan Zhou, Tao Xie, Youqing Shen
Summary: Nanomedicines, composed of carrier materials and small amounts of active pharmaceutical ingredients, have been widely used to improve therapeutic effects and reduce side effects. Converting hydrophobic/hydrophilic drugs into prodrugs capable of self-assembly into nanostructures offers many advantages, including high drug loading efficiency and controlled release. This review comprehensively summarizes recent advances in APDs and their nanomedicines, as well as the challenges and future prospects.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Article
Chemistry, Multidisciplinary
Keli An, Xuqian Deng, Hongli Chi, Yuchao Zhang, Yan Li, Ming Cheng, Zhigang Ni, Zhi Yang, Chao Wang, Jinling Chen, Jianbo Bai, Chunyan Ran, Yong Wei, Juan Li, Penghui Zhang, Feng Xu, Weihong Tan
Summary: Proteolysis Targeting Chimeras (PROTACs) are a promising therapeutic modality for tackling undruggable and resistant issues in drug discovery. Researchers have developed a generalized caging strategy to synthesize stimuli-responsive PROTACs (sr-PROTACs) that can be activated and released in response to specific pathological cues and external triggers. These sr-PROTACs showed high solubility, long plasma exposure, and efficient protein degradation in tumor cells, making them potential candidates for personalized treatment and tissue engineering.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Biochemistry & Molecular Biology
Yu Zhang, Wenliang Song, Yiming Lu, Yixin Xu, Changping Wang, Deng-Guang Yu, Il Kim
Summary: This work discusses the research progress and applications of poly(alpha-L-glutamic acid) (PGA) and its nanomaterials in drug delivery. It is found that PGA has biocompatibility and biodegradability, making it a promising candidate for drug delivery systems.
Article
Materials Science, Biomaterials
Viktor Eriksson, Jules Mistral, Ting Yang Nilsson, Markus Andersson Trojer, Lars Evenas
Summary: Functional textiles is a rapidly growing product segment where sustained release of actives is crucial. This study introduces microcapsules as a method to extend the release of active substances in textiles, compared to conventional impregnation methods. Encapsulated pyrene shows a significantly lower diffusion coefficient compared to impregnated pyrene, demonstrating the barrier properties of microcapsules that can prolong the potential functionality from hours to weeks.
JOURNAL OF MATERIALS CHEMISTRY B
(2023)
Review
Medicine, Research & Experimental
Aparajita Ghosh, Ambati Himaja, Swati Biswas, Onkar Kulkarni, Balaram Ghosh
Summary: Epigenetic modifications can alter gene expression at the transcriptional level, and dysregulation of these processes can lead to diseases such as cancer and metabolic disorders. Finding medications that target these modifications is of promising therapeutic interest, but very few have been approved for clinical use. This article provides a comprehensive review of recent advances in epigenetic therapeutics for cancer, with a focus on emerging delivery and development strategies.
MOLECULAR PHARMACEUTICS
(2023)
Article
Chemistry, Physical
Emiliane Daher Pereira, Sabu Thomas, Fernando Gomes de Souza Junior, Jessica da Silva Cardoso, Sergio Thode Filho, Vitor Correa da Costa, Fabiola da Silveira Maranhao, Nathali Ricardo Barbosa de Lima, Fernanda Veloso de Carvalho, Mostafa Galal Aboelkheir
Summary: The controlled drug delivery system, prepared by inserting ibuprofen and magnetite nanoparticles into the PLA matrix, combines the advantages of kinetic control (polymer) and spatial control (magnetite) to improve patient compliance and comfort, making the treatment more efficient. Various tests were conducted to verify the capacity of the system, showing sustained drug release profile and unchanged magnetic force of the nanoparticles in the PLA/drug systems.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Review
Biotechnology & Applied Microbiology
Lingling Huang, Jianmiao Yang, Tiantian Wang, Jianqing Gao, Donghang Xu
Summary: Lipidic prodrugs are an effective strategy to optimize the properties of therapeutic agents in cancer treatment, improving their physicochemical properties and antitumor activities while reducing systemic toxicity. However, the rational design of small-molecule lipidic prodrugs has not received enough attention. This review provides an overview of conjugation strategies for small-molecule lipidic prodrugs fabrication and highlights their rational design in response to physiological barriers of chemotherapeutic agents.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Valentina Di Francesco, Martina Di Francesco, Paolo Decuzzi, Roberto Palomba, Miguel Ferreira
Summary: By conjugating MTX with DSPE and PEG, researchers proposed two strategies to efficiently encapsulate MTX into liposomal particles, improving its bioavailability. These formulations represent an initial step towards the development of tailored targeted liposomes or particles for specific applications of MTX.
Article
Pharmacology & Pharmacy
Milica Markovic, Moran Zur, Noa Fine-Shamir, Ester Haimov, Isabel Gonzalez-Alvarez, Arik Dahan
Article
Chemistry, Medicinal
Jagadeesh Nagendra Manda, Milica Markovic, Ellen M. Zimmermann, Shimon Ben-Shabat, Arik Dahan, Aaron Aponick
Article
Pharmacology & Pharmacy
Milica Markovic, Moran Zur, Arik Dahan, Sandra Cvijic
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2020)
Article
Pharmacology & Pharmacy
Milica Markovic, Moran Zur, Inna Ragatsky, Sandra Cvijic, Arik Dahan
Review
Virology
Prasanta K. Dash, Santhi Gorantla, Larisa Poluektova, Mahmudul Hasan, Emiko Waight, Chen Zhang, Milica Markovic, Benson Edagwa, Jatin Machhi, Katherine E. Olson, Xinglong Wang, R. Lee Mosley, Bhavesh Kevadiya, Howard E. Gendelman
Summary: Humanized mice models are commonly used in research of infectious, degenerative, and cancer disorders, reflecting various molecular pathways affecting disease pathobiology. These models allow for long-term engraftments of human progenitor cells and high levels of human hematolymphoid reconstitution, enabling investigations into human pathobiology and therapeutic efficacy. They serve as cost-effective tools for studying infection or degeneration, with the ability to mimic natural pathogen host cells and test disease transmission and eradication.
Article
Pharmacology & Pharmacy
Arik Dahan, Daniel Porat, Milica Markovic, Moran Zur, Olga Kister, Peter Langguth
Summary: Experimental validation of the regional-dependent drug absorption changes after bariatric surgery provides important data for predicting drug absorption. It is crucial to consider the permeability of different intestinal segments post-surgery in simulation predictions to more accurately predict drug absorption after gastric bypass.
Article
Biochemistry & Molecular Biology
Jatin Machhi, Pravin Yeapuri, Milica Markovic, Milankumar Patel, Wenhui Yan, Yaman Lu, Jacob D. Cohen, Mahmudul Hasan, Mai Mohamed Abdelmoaty, You Zhou, Huangui Xiong, Xinglong Wang, R. Lee Mosley, Howard E. Gendelman, Bhavesh D. Kevadiya
Summary: Alzheimer's disease is the most common neurodegenerative disorder characterized by the deposition of amyloid beta plaques and neurofibrillary tangles. Cerium oxide nanoparticles have shown potential in reducing these pathological features and improving the pathobiology. Europium-doped cerium oxide nanoparticles can enhance cellular immune homeostasis and attenuate inflammation.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Milica Markovic, Karina Abramov-Harpaz, Clil Regev, Shimon Ben-Shabat, Aaron Aponick, Ellen M. M. Zimmermann, Yifat Miller, Arik Dahan
Summary: This study aimed to develop a drug delivery method that specifically targets inflamed sites in the gastrointestinal tract. Through in vitro and in vivo experiments as well as molecular dynamics simulation, it was found that PLC conjugates with a 12-carbon linker length had better prodrug activation compared to shorter linker lengths. This study provides a new mechanistic approach for future prodrug optimization and targeted drug therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Milica Markovic, Suyash Deodhar, Jatin Machhi, Pravin Yeapuri, Maamoon Saleh, Benson J. Edagwa, Rodney Lee Mosley, Howard E. Gendelman
Summary: Prodrugs are drug derivatives that are metabolized into pharmacologically active drugs. They are designed to overcome obstacles faced by parent drugs and improve treatment efficacy. Recent developments have shown the potential of prodrugs in treating neurodegenerative, inflammatory, and infectious diseases.
Article
Pharmacology & Pharmacy
Milica Markovic, Shimon Ben-Shabat, Jagadeesh Nagendra Manda, Karina Abramov-Harpaz, Clil Regev, Yifat Miller, Aaron Aponick, Ellen M. Zimmermann, Arik Dahan
Summary: This study developed a prodrug using phospholipid to specifically target and treat inflammation in the gastrointestinal tract. The prodrug was activated by the enzyme phospholipase A(2), which is overexpressed in diseased tissues. The results showed successful activation of the prodrug in diseased tissues, validating the drug targeting strategy.
Editorial Material
Chemistry, Multidisciplinary
Pravin Yeapuri, Katherine E. Olson, Yaman Lu, Mai Mohamed Abdelmoaty, Krista L. Namminga, Milica Markovic, Jatin Machhi, R. Lee Mosley, Howard E. Gendelman
Summary: The transformation of effector T cells into regulatory T cells has been shown to restore immunological balance and attenuate neurodegenerative diseases. In this study, mRNA lipid nanoparticles encoding an extended half-life albumin-GM-CSF fusion protein were developed and tested in preclinical models of Parkinson's disease, demonstrating immunomodulatory and neuroprotective effects.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Multidisciplinary Sciences
Suyash Deodhar, Brady Sillman, Aditya N. Bade, Sean N. Avedissian, Anthony T. Podany, JoEllyn M. McMillan, Nagsen Gautam, Brandon Hanson, Bhagya L. Dyavar Shetty, Adam Szlachetka, Morgan Johnston, Michellie Thurman, Daniel J. Munt, Alekha K. Dash, Milica Markovic, Arik Dahan, Yazen Alnouti, Alborz Yazdi, Bhavesh D. Kevadiya, Siddappa N. Byrareddy, Samuel M. Cohen, Benson Edagwa, Howard E. Gendelman
Summary: Ultra-long-acting integrase strand transfer inhibitors were developed through screening a library of nanoformulations. One particular nanocrystal showed potential for yearly dosing, releasing drugs slowly at the injection site and adjacent tissues. Significant plasma drug levels were maintained up to a year after injection.
NATURE COMMUNICATIONS
(2022)
Review
Neurosciences
Maamoon Saleh, Milica Markovic, Katherine E. Olson, Howard E. Gendelman, R. Lee Mosley
Summary: Dysregulation of immune system can lead to protein misfolding and aggregation in Parkinson's disease. Various strategies are being explored to improve clinical outcomes, including vaccines, antibodies, and gene therapy.
JOURNAL OF PARKINSONS DISEASE
(2022)
Article
Pharmacology & Pharmacy
Milica Markovic, Moran Zur, Sapir Garsiani, Daniel Porat, Sandra Cvijic, Gordon L. Amidon, Arik Dahan
Summary: The study aimed to evaluate the intestinal permeability mechanisms of minoxidil, with a focus on paracellular transport, and determine its suitability as a reference drug for the Biopharmaceutics Classification System (BCS). The results indicated that paracellular transport plays a significant role in the intestinal permeability of minoxidil following oral administration.
Meeting Abstract
Gastroenterology & Hepatology
Christopher Broxson, Milica Markovic, Arik Dahan, Shimon Ben-Shabat, Bikash Sahay, Ellen M. Zimmermann