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Related Concept Videos

Bioavailability Enhancement: Drug Permeability Enhancement01:27

Bioavailability Enhancement: Drug Permeability Enhancement

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Body:After oral administration, poor permeability often limits the rate at which drugs are absorbed through the intestinal epithelium. Enhancing drug permeability is crucial for effective therapy, and several strategies have been developed to overcome this challenge.One effective strategy involves the use of lipid-based formulations. These formulations enhance dissolution and solubility, targeting physiological mechanisms to increase drug absorption. This includes stimulating bile salt...
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Site-Targeted Drug Delivery Systems: Polymeric Carriers01:24

Site-Targeted Drug Delivery Systems: Polymeric Carriers

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Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...
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Bioavailability Enhancement: Drug Stability Enhancement and GI Retention01:05

Bioavailability Enhancement: Drug Stability Enhancement and GI Retention

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Body:Improving a drug's stability in the gastrointestinal (GI) tract is paramount for enhancing its bioavailability and therapeutic effectiveness. Various strategies are employed to protect the drug from the harsh gastric milieu and to ensure its release and absorption at the desired site within the GI tract.Polymer coatings are one such method used to shield drugs from the stomach's acidic environment. By preventing premature drug release, these coatings improve the bioavailability of unstable...
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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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Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry01:20

Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry

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Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...
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Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles
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Polymer therapeutics and the EPR effect.

Hiroshi Maeda1,2

  • 1a Kumamoto University and BioDynamic Research Foundation , Kumamoto , Japan.

Journal of Drug Targeting
|October 10, 2017
PubMed
Summary

The enhanced permeability and retention (EPR) effect, crucial for drug delivery, arises from vascular defects in tumors and inflammation. This phenomenon allows macromolecules to accumulate and persist in tumors for weeks, enabling targeted therapies.

Keywords:
EPR effecthistory of EPR effectinflammation/infectiontime and MW dependenttumor vascular permeability

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Area of Science:

  • Biomedical science
  • Pathophysiology
  • Pharmacology

Background:

  • The enhanced permeability and retention (EPR) effect describes the unique vascular properties in tumors and inflamed tissues.
  • Its origins trace back to studies on bacterial infections and edema, involving mediators like bradykinin, nitric oxide, and superoxide.

Purpose of the Study:

  • To review the historical development and underlying mechanisms of the EPR effect.
  • To highlight the application of the EPR effect in macromolecular drug delivery for cancer therapy.

Main Methods:

  • Historical review of scientific literature on vascular pathology and drug delivery.
  • Analysis of molecular mediators involved in extravasation and vascular permeability.
  • Case study of SMANCS (a polymer-drug conjugate) demonstrating EPR effect in vivo.

Main Results:

  • The EPR effect is driven by architectural defects in tumor vasculature and inflammatory processes.
  • Key mediators identified include bradykinin, nitric oxide, superoxide, and peroxynitrite.
  • Macromolecular drugs exhibit enhanced permeability and prolonged retention (days to weeks) in tumors.

Conclusions:

  • The EPR effect is a critical pathophysiological event with significant implications for targeted drug delivery.
  • Understanding and leveraging the EPR effect can improve the efficacy of macromolecular therapeutics in oncology.
  • Professor Ruth Duncan significantly contributed to the early dissemination of the EPR concept in polymer therapeutics.