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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
Published on: October 17, 2013
Paracellular drug absorption enhancement through tight junction modulation
Hendrik J R Lemmer1, Josias H Hamman
1North-West University, Unit for Drug Research and Development, Private Bag X6001, Potchefstroom, 2520, South Africa.
Expert Opinion on Drug Delivery
|November 21, 2012
Summary
Absorption enhancers can improve drug bioavailability by temporarily loosening intestinal tight junctions. This facilitates paracellular drug absorption, offering potential for oral delivery of poorly permeable drugs.
Area of Science:
- Pharmacology
- Drug Delivery
- Biophysics
Background:
- Improving oral bioavailability of poorly permeable drugs is a significant challenge in pharmaceutical development.
- Tight junctions form a regulated barrier in the intestinal epithelium, controlling paracellular transport.
- Absorption-enhancing agents can modulate tight junctions to facilitate drug permeation.
Purpose of the Study:
- To discuss the physiology and modulation of intestinal tight junctions.
- To review various agents that can alter tight junction permeability.
- To highlight the potential and challenges of using tight junction modulators for enhanced drug delivery.
Main Methods:
- Review of tight junction physiology and regulatory mechanisms.
- Discussion of different classes of tight junction modulators.
- Examples of modulators: ethylenediaminetetraacetic acid, chitosan, zonula occludens toxin, Aloe vera gel.
Main Results:
- Tight junction modulation offers a pathway to enhance paracellular drug absorption.
- Various agents, including chelating agents, polymers, toxins, and plant materials, can affect tight junction integrity.
- Understanding tight junction function is key to advancing drug delivery.
Conclusions:
- Tight junction modulation presents a promising strategy for oral delivery of drugs with low membrane permeability.
- Advances in understanding tight junctions have led to improved paracellular drug delivery approaches.
- Clinical application of tight junction modulators requires overcoming existing formulation and delivery challenges.
Related Concept Videos
01:23Mechanisms of Drug Absorption: Paracellular, Transcellular, and Vesicular Transport
Drugs need to permeate cell membranes to reach their target sites after administration. Orally administered drugs must transcend intestinal epithelial membrane barriers to infiltrate the systemic circulation. Drugs with a molecular weight of less than 500 Daltons diffuse through gaps between neighboring cells, called paracellular pathways.
However, most drugs use the transcellular route, traversing directly through the cell membranes via two mechanisms: passive and active transport. Passive...
However, most drugs use the transcellular route, traversing directly through the cell membranes via two mechanisms: passive and active transport. Passive...
01:29Tight Junctions
Tight junctions are molecular seals between cells that prevent the leaking of fluids, ions, and other small solutes across cavities and compartments in multicellular organisms. They are mainly composed of claudin and occludin transmembrane proteins, and other proteins such as tricellulin and JAM (junctional adhesion molecule). All these proteins are 4-pass transmembrane proteins, except JAM, which is a single-pass transmembrane protein belonging to the immunoglobulin superfamily. The...
01:27Bioavailability Enhancement: Drug Permeability Enhancement
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 secretion,...
01:24Cellular Membranes and Drug Transport
Drugs must traverse multiple biological barriers, such as multi-layered skin, single-layered intestinal epithelium, and the plasma membrane, to reach their target sites within the body. The plasma membrane, a highly structured composite of phospholipids, carbohydrates, and proteins, is the cell's protective boundary, facilitating selective substance exchange.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
01:23Drug Absorption Mechanism: Passive Membrane Transport
Passive transport is a method of drug absorption where small, lipid-soluble drugs can move across the cell membrane. This movement happens along the concentration gradient, which is a natural flow from higher to lower concentration areas. The speed at which the drug moves is directly related to its lipid–water partition coefficient. This means that the more a drug dissolves in lipids, the faster it diffuses or spreads throughout the body. It is important to note that most drugs are either weak...
01:06Carrier-Mediated Transport
Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...