The review covers the principles of creation of prodrugs as a chemical system for delivering drugs to targets. It presents the strategy of prodrug design and describes the main approaches to creation of prodrugs for drugs of different classes: antibiotics, anti-inflammatory and antitumour agents, corticosteroids, agents of the central action, etc.
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Med Res Rev
December 2024
Department of Medicinal Chemistry, Laboratory of Medicinal Chemical Biology, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Traditional prodrug strategies have been leveraged to overcome many inherent drawbacks of active native drugs in the drug research and development. However, endogenous stimuli such as specific microenvironment or enzymes are relied on to achieve the prodrug activation, resulting in unintended drug release and systemic toxicity. Alternatively, bioorthogonal cleavage reaction-enabled bioorthogonal prodrugs activation via exogenous triggers has emerged as a valuable approach, featuring spatiotemporally controlled drug release.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Department of Pharmaceutical Chemistry, M.R. College of Pharmaceutical Sciences and Research, Balisha-743234, India. Electronic address:
With cancer rates on the rise around the world, cancer treatment has dominated scientific discussions in recent years. The toxicity of cytotoxic drugs, their lack of tumor localization, and their uniform dispersion into tumor tissues are the obstacles to cancer therapy. Other cancer treatment drawbacks include short blood circulation half-lives and undesirable pharmacokinetic behavior.
View Article and Find Full Text PDFACS Nano
December 2024
Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Translational Medicine Laboratory, The First Affiliated Hospital of Wenzhou Medical University institution, Wenzhou, Zhejiang 325035, China.
Periodontitis is characterized by dysbiotic biofilms, gingival inflammation, and bone resorption, highlighting the urgent need for a comprehensive approach to drug combination therapy. In this study, we introduce dynamic covalent nanonetworks (dcNNWs) synthesized through a one-pot, four-component reaction-induced self-assembly method using polyamines, 2-formylphenylboronic acid, epigallocatechin gallate, and alendronate. The formation of iminoboronate bonds drives the creation of dcNNWs, allowing controlled release in the periodontitis microenvironment.
View Article and Find Full Text PDFEur J Pharm Biopharm
November 2024
Laboratory of Pharmaceutical Technology and Biopharmacy, CIRM, Université de Liège, 4000 Liège, Belgium.
High solubility in water and physiological fluids is an indispensable requirement for the pharmacological efficacy of an active pharmaceutical ingredient. Indeed, it is well established that pharmaceutical substances exhibiting limited solubility in water are inclined towards diminished and inconsistent absorption following oral administration, consequently resulting in variability in therapeutic outcomes. The current advancements in combinatorial chemistry and pharmaceutical design have facilitated the creation of drug candidates characterized by increased lipophilicity, elevated molecular size, and reduced aqueous solubility.
View Article and Find Full Text PDFInt J Pharm
August 2024
Department of Orthopaedics, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541000, China. Electronic address:
Rhein, a natural anthraquinone compound derived from traditional Chinese medicine, exhibits potent anti-inflammatory properties via modulating the level of Reactive oxygen or nitrogen species (RONS). Nevertheless, its limited solubility in water, brief duration of plasma presence, as well as its significant systemic toxicity, pose obstacles to its in vivo usage, necessitating the creation of a reliable drug delivery platform to circumvent these difficulties. In this study, an esterase-responsive and mitochondria-targeted nano-prodrug was synthesized by conjugating Rhein with the polyethylene glycol (PEG)-modified triphenyl phosphonium (TPP) molecule, forming TPP-PEG-RH, which could spontaneously self-assemble into RPT NPs when dispersed in aqueous media.
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