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Related Concept Videos

Methods for Studying Drug Absorption: In vitro01:16

Methods for Studying Drug Absorption: In vitro

284
In vitro experiments are crucial for understanding the transport and absorption of drugs through biological materials. These studies employ varied methods such as the diffusion cell method, the everted sac technique, and the everted ring technique.
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
284
Methods for Studying Drug Absorption: In situ01:09

Methods for Studying Drug Absorption: In situ

318
In situ experiments, such as the Doluisio method and Single-Pass Perfusion technique, provide critical insights into drug uptake by simulating in vivo conditions for drug absorption.
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
318
One-Compartment Open Model for Extravascular Administration: First-Order Absorption Model01:15

One-Compartment Open Model for Extravascular Administration: First-Order Absorption Model

277
The first-order absorption model for extravascular administration describes the rate at which a drug is absorbed and eliminated, following the principles of first-order kinetics. This model is vital as it provides a mathematical representation of drug behavior within the body. It also allows for the prediction and interpretation of drug absorption and elimination based on the rate of change in drug concentration over time. This model can be visualized as a plasma concentration-time profile...
277
Non-Oral Extravascular Drug Absorption Routes01:15

Non-Oral Extravascular Drug Absorption Routes

262
Non-oral extravascular routes, which encompass sublingual, buccal, topical, intramuscular, and inhalation methods, primarily utilize passive diffusion to transport drugs into the systemic circulation. The absorption rates and effectiveness of these routes depend on the drug's physicochemical properties, as well as the patient's anatomical and pathophysiological state.
Lipophilic drugs that are stable at salivary pH (6) and exhibit minimal binding to the oral mucosa are absorbed more...
262
Physiological Pharmacokinetic Models: Blood Flow-Limited Versus Diffusion-Limited Models00:57

Physiological Pharmacokinetic Models: Blood Flow-Limited Versus Diffusion-Limited Models

135
Physiological pharmacokinetic models, often called flow-limited or perfusion models, typically assume a swift drug distribution between tissue and venous blood, creating a rapid drug equilibrium. This premise is based on the idea that drug diffusion is extremely fast, and the cell membrane presents no barrier to drug permeation. In this scenario, where no drug binding occurs, the drug concentration in the tissue equals that of the venous blood leaving the tissue. This greatly simplifies the...
135
One-Compartment Open Model for Extravascular Administration: Zero-Order Absorption Model01:12

One-Compartment Open Model for Extravascular Administration: Zero-Order Absorption Model

140
Extravascular administration, such as oral or intramuscular routes, is a non-invasive drug delivery method, often preferred for ease and patient compliance. A key factor here is absorption, which dictates how quickly and effectively the drug enters the bloodstream from the administration site. Absorption follows either zero-order or first-order kinetics.
Zero-order absorption maintains a steady rate irrespective of the amount of drug left to be absorbed, making it a constant process. In the...
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Related Experiment Video

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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
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Microphysiological endothelial models to characterize subcutaneous drug absorption.

Giovanni S Offeddu1, Jean Carlos Serrano2, Zhengpeng Wan1

  • 1Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

ALTEX
|December 19, 2022
PubMed
Summary

This study introduces a human hypodermal microphysiological model to understand protein drug bioavailability. This new model aids in predicting drug performance before clinical trials, improving patient access to therapies.

Keywords:
blood and lymphatic absorptionmicrofluidic skin-on-chipmonoclonal antibodiespreclinical modelssubcutaneous administration

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Area of Science:

  • Biomedical Engineering
  • Pharmacology
  • Cell Biology

Background:

  • Subcutaneous bioavailability of protein therapeutics exhibits high variability, hindering patient access to novel treatments.
  • Existing preclinical models lack physiological relevance for studying human bioavailability.
  • Understanding the hypodermal microenvironment is crucial for optimizing protein drug delivery.

Purpose of the Study:

  • To develop a microphysiological model of the human hypodermal vasculature.
  • To investigate the factors within the injection site microenvironment influencing protein therapeutic bioavailability.
  • To provide a physiologically relevant platform for preclinical assessment of subcutaneous drug delivery.

Main Methods:

  • Constructed a three-dimensional, perfusable microvessel model using human dermal endothelial cells, fibroblasts, and adipocytes.
  • Incorporated relevant extracellular matrix components into the model.
  • Measured biophysical parameters within the hypodermal microenvironment impacting protein kinetics and distribution.

Main Results:

  • The model successfully replicated key features of the human hypodermal microenvironment.
  • Demonstrated the ability to measure critical biophysical parameters affecting protein drug behavior.
  • Validated the model's utility for studying protein-microenvironment interactions.

Conclusions:

  • Microphysiological models of the subcutaneous space offer a promising approach for preclinical drug development.
  • This model can aid in optimizing subcutaneous administration of protein therapeutics for improved bioavailability.
  • Facilitates better prediction of in vivo drug performance, potentially reducing development timelines and costs.