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Prodrugs

Prodrugs

Prodrugs are a class of pharmaceutical compounds that undergo a biotransformation process within the body to be converted into a pharmacologically active drug. Prodrugs are designed to improve the therapeutic properties of the parent drug, such as enhancing bioavailability, increasing stability, or reducing toxicity. The concept of prodrugs revolves around modifying the chemical structure of the original drug to make it more effective or convenient for administration.
Prodrugs help overcome...

Drug Metabolism: Phase II Reactions

Drug Metabolism: Phase II Reactions

Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...

Drug Biotransformation: Overview

Drug Biotransformation: Overview

Pharmaceutical substances known as xenobiotics are predominantly lipophilic and nonionized. This enables them to permeate lipid bilayers, such as cell membranes, and interact with intracellular target receptors. Lipophilic drugs have an advantage in crossing biological barriers and reaching their intended sites of action. However, lipophilic drugs often have a restricted capacity for renal expulsion or elimination from the body. When these drugs enter the kidneys and undergo glomerular...

Drug Biotransformation: Overview

Drug Biotransformation: Overview

Biotransformation, also known as drug metabolism, is a vital physiological process that chemically alters drugs, facilitating their elimination from the body and terminating their action. This process involves two main phases: phase I and phase II reactions. Phase I reactions, including oxidation, reduction, and hydrolysis, introduce or unmask polar functional groups on the drug molecule, thereby increasing its water solubility. By enhancing water solubility, the drug becomes more hydrophilic...

Modified-Release Drug Delivery Systems: Site-Targeted

Modified-Release Drug Delivery Systems: Site-Targeted

Site-targeted drug delivery systems enhance therapeutic efficacy while minimizing systemic toxicity and treatment costs. Unlike conventional methods, these systems ensure precise drug delivery, improving bioavailability and reducing side effects. Targeted drug delivery is classified into three levels. First-order targeting directs drugs to the capillary beds of specific organs or tissues. Second-order targets specific cell types, such as tumor cells, using receptor-mediated interactions.

Phase II Reactions: Sulfation and Conjugation with α-Amino Acids

Phase II Reactions: Sulfation and Conjugation with α-Amino Acids

Sulfation and α-amino acid conjugation are two critical biotransformation reactions in drug metabolism. Sulfation, a phase II biotransformation reaction, involves adding a polar sulfate group to a drug, enhancing its water solubility and promoting excretion. This process can either co-occur with or occur independently of glucuronidation. Nonmicrosomal sulfotransferase enzymes catalyze the process. The reaction involves 3'-phosphoadenosine-5'-phosphosulfate or PAPS coenzyme activation, sulfur...

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Related Experiment Video

Updated: May 16, 2026

Facile Preparation and Photoactivation of Prodrug-Dye Nanoassemblies

Facile Preparation and Photoactivation of Prodrug-Dye Nanoassemblies

Published on: February 17, 2023

Substrate mediated enzyme prodrug therapy.

Betina Fejerskov¹, Alexander N Zelikin

¹Department of Chemistry, Aarhus University, Aarhus, Denmark.

|November 16, 2012

Summary

Substrate Mediated Enzyme Prodrug Therapy (SMEPT) uses enzyme-coated surfaces to convert prodrugs into active drugs locally. This novel drug delivery method enables controlled therapeutic release for applications in tissue engineering and beyond.

Area of Science:

Biomaterials Science
Drug Delivery Systems
Enzyme Engineering

Background:

Current drug delivery methods face challenges in achieving localized therapeutic effects and minimizing systemic toxicity.
Enzyme-functionalized materials offer potential for targeted drug activation and release.
Prodrug strategies are crucial for improving drug solubility, stability, and targeted activation.

Purpose of the Study:

To introduce and demonstrate the efficacy of Substrate Mediated Enzyme Prodrug Therapy (SMEPT) as a novel, localized drug delivery system.
To establish proof-of-concept for SMEPT using enzyme-functionalized hydrogel substrates and prodrugs.
To evaluate the controlled release, cellular uptake, and therapeutic effect of SMEPT in vitro.

Main Methods:

Development of micro-structured poly(vinyl alcohol) hydrogels functionalized with β-glucuronidase.

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Validation of Therapeutic Agent Conjugation to Polyvinyl Alcohol-Coated Medical Devices

Validation of Therapeutic Agent Conjugation to Polyvinyl Alcohol-Coated Medical Devices

Published on: November 29, 2024

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Last Updated: May 16, 2026

Facile Preparation and Photoactivation of Prodrug-Dye Nanoassemblies

Facile Preparation and Photoactivation of Prodrug-Dye Nanoassemblies

Published on: February 17, 2023

Validation of Therapeutic Agent Conjugation to Polyvinyl Alcohol-Coated Medical Devices

Validation of Therapeutic Agent Conjugation to Polyvinyl Alcohol-Coated Medical Devices

Published on: November 29, 2024

Utilizing glucuronide prodrugs for localized conversion into active therapeutics upon enzymatic cleavage.

Co-culturing hepatic cells (HepG2) with the functionalized hydrogels to assess drug uptake and cytotoxicity.

Employing a model fluorescent cargo and an anticancer drug derivative (SN-38 glucuronide) to evaluate release kinetics and therapeutic efficacy.

Main Results:

Demonstrated enzymatic activity of the hydrogel-based system and controlled release of fluorescent cargo.
Confirmed that SMEPT is compatible with adhering cells and facilitates time- and dose-dependent cargo uptake by HepG2 cells.
Showed that SMEPT with SN-38 glucuronide prodrug effectively reduced cancer cell viability, comparable to the parent drug.
Established dose-dependent responses, indicating external control over drug delivery via the functionalized surface.

Conclusions:

SMEPT represents a highly adaptable platform for localized drug delivery, utilizing enzyme-functionalized substrates for controlled prodrug conversion.
The system demonstrated effective in situ drug generation, cellular uptake, and therapeutic efficacy, with external control over drug release.
SMEPT holds significant promise for diverse biomedical applications, particularly in surface-mediated drug delivery and tissue engineering.