TITLE:
Exploring Ester Prodrugs: A Comprehensive Review of Approaches, Applications, and Methods
AUTHORS:
Guangyang Zhou
KEYWORDS:
Ester Prodrugs, Solubility, Bioavailability, Stability, Ester Prodrug Approaches, Simple Ester Prodrugs, Amino Acid Ester Prodrugs, Sugar Ester Prodrugs, Lipid Ester Prodrugs, Polymeric Ester Prodrugs, Esterase-Responsive Nanoparticles, Hydrolysis, Cancer Treatment, Cardiovascular Diseases, Neurological Disorders
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.15 No.8,
August
27,
2024
ABSTRACT: The review provides an overview of the approaches, applications, and methods for ester prodrugs. Ester prodrugs are pharmacologically inactive compounds in their original form but become active drugs on biotransformation within the body, which offers advantages concerning the solubility, stability, and targeted delivery of the active drug. Several approaches of ester prodrugs have been reviewed in this review, including simple ester prodrugs, amino acid ester prodrugs, sugar ester prodrugs, lipid ester prodrugs, and polymeric ester prodrugs. This review incorporates in vitro and in vivo methods as well as the characterization of physical and chemical properties for ester prodrugs, cell culture systems, enzymatic assays, and animal models—all of these having a very important bearing on the evaluation of stability, bioavailability, and efficacy for ester prodrugs. While the benefits of using ester prodrugs are significant, there are also disadvantages like instability, poor or variable enzymatic hydrolysis, and toxicity from released promoieties or by-products. This review discusses solutions to the various limitations that include enhancing stability with ionizable promoieties and using physiologically-based pharmacokinetic modeling. The review also highlights the application of ester prodrugs in neurological disorders, such as Parkinson’s disease, and the ongoing efforts to address the critical limitations in treatment efficacy. Future prodrug strategies are poised to advance significantly by harnessing diverse transport mechanisms across the blood-brain barrier and integrating nanotechnology.