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Modified-Release Drug Delivery Systems: Stimuli-Activated01:30

Modified-Release Drug Delivery Systems: Stimuli-Activated

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Stimuli-activated drug delivery systems are designed to release drugs in response to specific physical, chemical, or biological stimuli. These systems often utilize hydrogels—three-dimensional, hydrophilic polymer networks capable of swelling in aqueous environments and retaining significant fluid volumes. Upon exposure to particular stimuli, these hydrogels undergo structural transitions that allow the embedded drug to be released. Due to this adaptive behavior, such systems are also...
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Modified-Release Drug Delivery Systems: Classification01:23

Modified-Release Drug Delivery Systems: Classification

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Modified-release drug delivery systems improve drug efficacy and minimize side effects by controlling the rate and location of drug release. These systems fall into three categories: rate-programmed, stimuli-activated, and site-targeted.Rate-programmed systems release drugs at a predetermined rate, maintaining consistent therapeutic levels and reducing fluctuations that could lead to toxicity or subtherapeutic effects. These systems use polymeric matrices, reservoir-based designs, or osmotic...
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Modified-Release Drug Delivery Systems: Rate-Programmed I01:22

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Rate-programmed drug delivery systems (DDS) are designed to release drugs at specific, controlled rates to maintain consistent therapeutic levels. These systems are categorized based on their release mechanisms, including dissolution-controlled DDS, diffusion-controlled DDS, and combined dissolution-diffusion-controlled DDS.In dissolution-controlled DDS, the release rate depends on the slow dissolution of the drug itself or the surrounding matrix. Drugs with inherently slow dissolution rates,...
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Modified-Release Drug Delivery Systems: Site-Targeted01:24

Modified-Release Drug Delivery Systems: Site-Targeted

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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.
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Modified-Release Drug Delivery Systems: Rate-Programmed II01:19

Modified-Release Drug Delivery Systems: Rate-Programmed II

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Rate-programmed drug delivery systems release drugs in a controlled manner to maintain therapeutic levels. Three main designs include reservoir, matrix, and hybrid systems.Reservoir systems consist of a drug core enclosed within a membrane that controls drug release. In non-swelling reservoir systems, polymers like ethyl cellulose or polymethacrylates are used. These do not hydrate in aqueous media and control release through membrane thickness, porosity, or insolubility. This type includes...
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Modified-Release Drug Delivery Systems: Influencing Factors01:20

Modified-Release Drug Delivery Systems: Influencing Factors

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Modified-release drug delivery systems are designed to optimize the therapeutic effect of drugs by minimizing side effects, reducing the dosage required, and controlling drug release to align with pharmacokinetic and pharmacodynamic needs. The system depends on two key factors: the drug's release from the formulation and its movement through the body to the target site. Unlike conventional dosage forms, where absorption is the limiting step, the rate of drug release is the key determinant in...
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Updated: Mar 25, 2026

Alternating Magnetic Field-Responsive Hybrid Gelatin Microgels for Controlled Drug Release
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Tunable pH-Sensitive Linker for Controlled Release.

Cindy J Choy1, Jonathan J Geruntho1, Austen L Davis1

  • 1Department of Chemistry, Washington State University , Pullman, Washington 99164-4630, United States.

Bioconjugate Chemistry
|February 18, 2016
PubMed
Summary
This summary is machine-generated.

We created novel pH-sensitive linkers that release drugs based on phosphoramidate chemistry. These linkers are tunable for controlled drug delivery without enzymes, responding solely to pH changes.

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Area of Science:

  • Biochemistry
  • Organic Chemistry
  • Materials Science

Background:

  • Controlled drug release systems are crucial for targeted therapies.
  • Existing systems often rely on enzymatic activity, limiting their application.
  • pH-sensitive linkers offer a promising alternative for triggered drug release.

Purpose of the Study:

  • To develop a novel pH-sensitive linker based on a phosphoramidate scaffold.
  • To enable tunable, enzyme-independent drug release at various pH values.
  • To explore applications in drug conjugates and intracellular delivery.

Main Methods:

  • Synthesis of phosphoramidate-based linkers with proximal acidic groups.
  • Investigation of the P-N bond hydrolysis mechanism.
  • Tuning linker stability and release rates based on amine pKa and scaffold modifications.

Main Results:

  • Developed phosphoramidate linkers responsive to pH alone.
  • Demonstrated intramolecular general-acid catalysis for P-N bond hydrolysis.
  • Showcased tunability of release rates by altering amine type and scaffold proximity.

Conclusions:

  • Phosphoramidate linkers offer a versatile platform for pH-triggered drug release.
  • These linkers can be tailored for specific applications, including antibody-drug conjugates and prodrugs.
  • The technology has broad applicability in controlled release and intracellular studies.