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Related Concept Videos

Modified-Release Drug Delivery Systems: Drug Release Characteristics01:22

Modified-Release Drug Delivery Systems: Drug Release Characteristics

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Drug release from modified-release dosage forms is designed to achieve specific therapeutic effects by controlling the rate and extent of drug release. The classification of these drug release systems is based on key pharmacokinetic assumptions: drug disposition follows first-order kinetics, drug release is the rate-limiting step in absorption, and the released drug is rapidly and completely absorbed.There are four major models of drug release patterns. The first model is the slow zero-order...
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Modified-Release Drug Delivery Systems: Overview01:19

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Modified-release dosage forms are designed to address the limitations of drugs with short biological half-lives. These forms maintain stable therapeutic drug concentrations over extended periods, reducing the need for frequent dosing. A consistent drug level helps minimize peak-trough fluctuations, which can reduce adverse effects, lower the risk of drug resistance, and improve overall treatment effectiveness.One common type of modified-release form is the extended-release (ER) formulation. ER...
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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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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 (MR) dosage forms are designed to extend drug release over time, thereby maintaining stable plasma concentrations and reducing dosing frequency. However, their bioavailability is typically below 100% due to incomplete drug release and presystemic metabolism, and limitations in drug permeability across the gastrointestinal epithelium, all of which can restrict the fraction of the drug reaching systemic circulation. Consequently, studying the in vivo bioavailability of MR...
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Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
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mRNA function after intracellular delivery and release.

Vladimir P Zhdanov1

  • 1Section of Biological Physics, Department of Physics, Chalmers University of Technology, Göteborg, Sweden; Boreskov Institute of Catalysis, Russian Academy of Sciences, Novosibirsk, Russia.

Bio Systems
|January 15, 2018
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Summary
This summary is machine-generated.

Nanocarrier delivery of messenger RNA (mRNA) enables transient gene regulation. The study finds that gene expression kinetics are surprisingly insensitive to mRNA release duration, regardless of release speed.

Keywords:
Drug deliveryGene expressionMean-field kinetic equationsSubcellular processes

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Area of Science:

  • Biotechnology
  • Molecular Biology
  • Systems Biology

Background:

  • Nanocarrier systems are crucial for delivering messenger RNA (mRNA) for protein translation.
  • Transiently expressed proteins, like transcription factors, can modulate cellular genetic networks.
  • Understanding mRNA release kinetics is key to controlling gene expression dynamics.

Purpose of the Study:

  • To theoretically investigate the impact of mRNA release kinetics on transient gene expression.
  • To analyze gene expression patterns in stable, bistable, and oscillatory regimes.
  • To determine the sensitivity of gene expression kinetics to mRNA release duration.

Main Methods:

  • Theoretical modeling of nanocarrier-mediated mRNA delivery and release.
  • Analysis of transient gene expression kinetics under different release scenarios (rapid vs. slow).
  • Examination of gene expression dynamics in various cellular states (stable, bistable, oscillatory).

Main Results:

  • mRNA release kinetics significantly influence transient gene expression features.
  • Gene expression exhibits distinct patterns in stable, bistable, and oscillatory regimes.
  • Transient kinetics show qualitative similarities irrespective of whether mRNA release is rapid or slow.
  • The duration of mRNA release has a lesser impact on transient gene expression kinetics than anticipated.

Conclusions:

  • Nanocarrier-mediated mRNA delivery offers a viable strategy for temporary genetic network regulation.
  • The transient kinetics of gene expression are robust and less dependent on mRNA release duration than expected.
  • These findings advance the understanding of mRNA-based therapeutics and gene modulation strategies.