Directed Enzyme Prodrug Therapies

Niculescu‐Duvaz, Dan; Negoita‐Giras, Gabriel; Niculescu‐Duvaz, Ion; Hedley, Douglas; Springer, Caroline J.

doi:10.1002/9783527633166.ch12

Cited by 7 publications

(1 citation statement)

References 306 publications

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“…Another exciting approach to prodrug targeting to specific tissues is the directed enzyme prodrug therapy (DEPT), which uses enzymes artificially brought into the body to activate the prodrug and release the active moiety. This strategy has been shown for antibodies (ADEPT), genes (GDEPT, also known as suicide gene therapy, where the enzyme is created inside the target cell, by means of a gene supplied by gene therapy), viruses (VDEPT, where viruses carry the gene for GDEPT), polymer-directed enzyme prodrug therapy (PDEPT), and clostridia-directed enzyme prodrug therapy (CDEPT), which takes advantage of the hypoxic cancer surroundings to target drugs to tumors through a bacteria residing in the cancer tissues [40].…”

Section: Prodrug Activationmentioning

confidence: 99%

Prodrugs for Improved Drug Delivery: Lessons Learned from Recently Developed and Marketed Products

2020

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Prodrugs are bioreversible, inactive drug derivatives, which have the ability to convert into a parent drug in the body. In the past, prodrugs were used as a last option; however, nowadays, prodrugs are considered already in the early stages of drug development. Optimal prodrug needs to have effective absorption, distribution, metabolism, and elimination (ADME) features to be chemically stable, to be selective towards the particular site in the body, and to have appropriate safety. Traditional prodrug approach aims to improve physicochemical/biopharmaceutical drug properties; modern prodrugs also include cellular and molecular parameters to accomplish desired drug effect and site-specificity. Here, we present recently investigated prodrugs, their pharmaceutical and clinical advantages, and challenges facing the overall prodrug development. Given examples illustrate that prodrugs can accomplish appropriate solubility, increase permeability, provide site-specific targeting (i.e., to organs, tissues, enzymes, or transporters), overcome rapid drug metabolism, decrease toxicity, or provide better patient compliance, all with the aim to provide optimal drug therapy and outcome. Overall, the prodrug approach is a powerful tool to decrease the time/costs of developing new drug entities and improve overall drug therapy.

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Section: Prodrug Activationmentioning

confidence: 99%

Prodrugs for Improved Drug Delivery: Lessons Learned from Recently Developed and Marketed Products

2020

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Targeted Prodrugs in Oral Drug Delivery

Marković

Ben‐Shabat

Dahan

2022

Targeted Drug Delivery

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Hybrid Enzyme‐Polymeric Capsules/Mesoporous Silica Nanodevice for In Situ Cytotoxic Agent Generation

Baeza

Guisasola

Torres‐Pardo

et al. 2014

Adv Funct Materials

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A novel nanocarrier based on functionalized mesoporous silica nanoparticles able to transport a non-toxic pro-drug and the enzyme responsible for its activation has been presented. This nanodevice is able to generate in situ cytotoxic species once accumulated in the tumoral cell.Enzymes are sensitive macromolecules which can suffer denaturalization in biological media due to the presence of proteases or other aggressive agents. Moreover, the direct attachment of enzymes to the silica surface could reduce their activity by conformational changes or active site blockage. For these reasons, in order to create a robust system able to work in living organisms, the enzymes were previously coated with a protective polymeric shell which allows the attachment on the silica surface preserving their activity. The efficacy of this hybrid nanodevice for antitumoral purposes has been tested against several human tumoral cells as neuroblastoma and leukemia showing significant efficacy. It converts this device in a promising candidate for further in vivo studies for oncology therapy.

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Directed Enzyme Prodrug Therapies

Cited by 7 publications

References 306 publications

Prodrugs for Improved Drug Delivery: Lessons Learned from Recently Developed and Marketed Products

Prodrugs for Improved Drug Delivery: Lessons Learned from Recently Developed and Marketed Products

Targeted Prodrugs in Oral Drug Delivery

Hybrid Enzyme‐Polymeric Capsules/Mesoporous Silica Nanodevice for In Situ Cytotoxic Agent Generation

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