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The Journal of Clinical Investigation May 2000
Review
Topics: Antineoplastic Agents; Genetic Therapy; Neoplasms; Prodrugs
PubMed: 10791987
DOI: 10.1172/JCI10001 -
ACS Nano Apr 2023Prodrug nanoassemblies combine the advantages of prodrug and nanomedicines, offering great potential in targeting the lesion sites and specific on-demand drug release,...
Prodrug nanoassemblies combine the advantages of prodrug and nanomedicines, offering great potential in targeting the lesion sites and specific on-demand drug release, maximizing the therapeutic performance while minimizing their side effects. However, there is still lacking a facile pathway to prepare the lipid prodrug nanoassemblies (LPNAs). Herein, we report the LPNAs via the dynamic covalent boronate between catechol and boronic acid. The resulting LPNAs possess properties like drug loading in a dynamic covalent manner, charge reversal in an acidic microenvironment, and specific drug release at an acidic and/or oxidative microenvironment. Our methodology enables the encapsulation and delivery of three model drugs: ciprofloxacin, bortezomib, and miconazole. Moreover, the LPNAs are often more efficient in eradicating pathogens or cancer cells than their free counterparts, both and . Together, our LPNAs with intriguing properties may boost the development of drug delivery and facilitate their clinical applications.
Topics: Prodrugs; Drug Delivery Systems; Bortezomib; Boronic Acids; Lipids; Nanoparticles; Drug Liberation
PubMed: 36999933
DOI: 10.1021/acsnano.2c12233 -
Molecules (Basel, Switzerland) Dec 2015Prodrug design is a widely known molecular modification strategy that aims to optimize the physicochemical and pharmacological properties of drugs to improve their... (Review)
Review
Prodrug design is a widely known molecular modification strategy that aims to optimize the physicochemical and pharmacological properties of drugs to improve their solubility and pharmacokinetic features and decrease their toxicity. A lack of solubility is one of the main obstacles to drug development. This review aims to describe recent advances in the improvement of solubility via the prodrug approach. The main chemical carriers and examples of successful strategies will be discussed, highlighting the advances of this field in the last ten years.
Topics: Biological Availability; Drug Delivery Systems; Drug Design; Prodrugs; Solubility
PubMed: 26729077
DOI: 10.3390/molecules21010042 -
Molecules (Basel, Switzerland) Mar 2010Reduced glutathione (GSH) is the most abundant non-protein thiol in mammalian cells and the preferred substrate for several enzymes in xenobiotic metabolism and... (Review)
Review
Reduced glutathione (GSH) is the most abundant non-protein thiol in mammalian cells and the preferred substrate for several enzymes in xenobiotic metabolism and antioxidant defense. It plays an important role in many cellular processes, such as cell differentiation, proliferation and apoptosis. GSH deficiency has been observed in aging and in a wide range of pathologies, including neurodegenerative disorders and cystic fibrosis (CF), as well as in several viral infections. Use of GSH as a therapeutic agent is limited because of its unfavorable biochemical and pharmacokinetic properties. Several reports have provided evidence for the use of GSH prodrugs able to replenish intracellular GSH levels. This review discusses different strategies for increasing GSH levels by supplying reversible bioconjugates able to cross the cellular membrane more easily than GSH and to provide a source of thiols for GSH synthesis.
Topics: Disease; Glutathione; Humans; Prodrugs
PubMed: 20335977
DOI: 10.3390/molecules15031242 -
Current Medicinal Chemistry 2010The prodrug design is a versatile, powerful method that can be applied to a wide range of parent drug molecules, administration routes, and formulations. Clinically, the... (Review)
Review
The prodrug design is a versatile, powerful method that can be applied to a wide range of parent drug molecules, administration routes, and formulations. Clinically, the majority of prodrugs are used with the aim of enhancing drug permeation by increasing lipophilicity, or by improving aqueous solubility. Prodrug design may improve the bioavailability of parent molecule, and thus can be integrated into the iterative process of lead optimization, rather than employing it as a post-hoc approach. The purpose of this review is to provide an update of advances and progress in the knowledge of current strategic approaches of prodrug design, along with their real-world utility in drug discovery and development. The review covers the type of prodrugs and functional groups that are amenable to prodrug design. Various prodrug approaches for improving oral drug delivery are discussed, with numerous examples of marketed prodrugs, including improved aqueous solubility, improved lipophilicity, transporter-mediated absorption, and prodrug design to achieve site-specific delivery. Tools employed for prodrug screening, and specific challenges in prodrug research and development are also elaborated. This article is intended to encourage discovery scientists to be creative and consider a rationally designed prodrug approach during the lead optimization phase of drug discovery programs, when the structure activity relationship (SAR) for the drug target is incompatible with pharmacokinetic or biopharmaceutical objectives.
Topics: Biological Availability; Clinical Trials as Topic; Drug Carriers; Drug Design; Membrane Transport Proteins; Prodrugs
PubMed: 20858214
DOI: 10.2174/092986710793205426 -
Journal of Medicinal Chemistry Dec 2023Time- and space-resolved drug delivery is highly demanded for cancer treatment, which, however, can barely be achieved with a traditional prodrug strategy. In recent... (Review)
Review
Time- and space-resolved drug delivery is highly demanded for cancer treatment, which, however, can barely be achieved with a traditional prodrug strategy. In recent years, the prodrug strategy based on a bioorthogonal bond cleavage chemistry has emerged with the advantages of high temporospatial resolution over drug activation and homogeneous activation irrespective of individual heterogeneity. In the past five years, tremendous progress has been witnessed in this field with one such bioorthogonal prodrug entering Phase II clinical trials. This Perspective aims to highlight these new advances (2019-2023) and critically discuss their pros and cons. In addition, the remaining challenges and potential strategic directions for future progress will also be included.
Topics: Prodrugs; Drug Delivery Systems
PubMed: 38085596
DOI: 10.1021/acs.jmedchem.3c01459 -
Current Topics in Medicinal Chemistry 2021
Topics: Drug Development; Prodrugs
PubMed: 34983338
DOI: 10.2174/156802662132211215162732 -
Advanced Drug Delivery Reviews Jul 2007Drug design in recent years has attempted to explore new chemical spaces resulting in more complex, larger molecular weight molecules, often with limited water... (Review)
Review
Drug design in recent years has attempted to explore new chemical spaces resulting in more complex, larger molecular weight molecules, often with limited water solubility. To deliver molecules with these properties, pharmaceutical scientists have explored many different techniques. An older but time-tested strategy is the design of bioreversible, more water-soluble derivatives of the problematic molecule, or prodrugs. This review explores the use of prodrugs to effect improved oral and parenteral delivery of poorly water-soluble problematic drugs, using both marketed as well as investigational prodrugs as examples. Prodrug interventions should be considered early in the drug discovery paradigm rather than as a technique of last resort. Their importance is supported by the increasing percentage of approved new drug entities that are, in fact, prodrugs.
Topics: Chemistry, Pharmaceutical; Drug Administration Routes; Drug Design; Prodrugs; Solubility; Structure-Activity Relationship; Water
PubMed: 17628203
DOI: 10.1016/j.addr.2007.05.013 -
Current Topics in Medicinal Chemistry 2021Uncaging chemistry catalyzed by transition metals is developed from deprotection reactions and metal-organic catalytic reactions. Also, it has the characteristics of... (Review)
Review
Uncaging chemistry catalyzed by transition metals is developed from deprotection reactions and metal-organic catalytic reactions. Also, it has the characteristics of high efficiency, simplicity and rapidity in the living biological system. In the past decade, metal encapsulation systems (such as nanoparticles) and metal complexes have been developed to reveal the reactivity of transition metals (including palladium, ruthenium, and gold) in biological systems. Metal nanostructures provide huge possibilities for targeted drug delivery, detection, diagnosis and imaging. So far, palladium, ruthenium and gold nano-architectures have dominated the field, but there are some problems that hinder their wide application in clinical practice. In this review, based on palladium, ruthenium, gold and their complexes, the application of prodrug design through uncaging reaction has been widely discussed.
Topics: Animals; Drug Design; Gold; Humans; Palladium; Prodrugs; Ruthenium
PubMed: 34170808
DOI: 10.2174/1568026621666210624113313 -
Signal Transduction and Targeted Therapy Jan 2022
Topics: Cell Hypoxia; Cell Line, Tumor; Humans; Immunoconjugates; Prodrugs
PubMed: 35058439
DOI: 10.1038/s41392-021-00833-8