Blood Simplfied

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Why the human bloodstream is important to pharmaceutical scientists

This lesson provides an overview of the circulatory system. We will learn what the blood is and how it transports nutrients to our body cells. Knowledge of the blood transport system is very important to scientists in pharmaceutical companies such as Elan Corporation plc., because drug treatments are also transported around the body in the blood.

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The method by which a pharmaceutical substance is administered to a person is known as drug delivery. The extent to which the drug is utilised effectively in the body is known as bioavailability. Whether treatments are taken by mouth, injection or inhalation bioavailability is improved if the substance is soluble in water. If it is not soluble, then it can not be delivered efficiently to the bloodstream.

Why do we need a transport system?

Because our tissues and cells are located in discrete locations throughout the body, the essential materials must be brought to them. Also, waste and other ‘export’ materials must be carried away. The materials are carried in a special liquid called blood. Some of these materials are carried in solution and some in suspension. Blood is the liquid that sustains our life.

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What is a cell?

A cell is the smallest organised structure that demonstrates the characteristics of life. Cells, although very small, are incredibly complex chemical factories taking in materials from their surroundings to sustain their existence and to make copies of themselves.

The cell is the fundamental sub-unit of the human body. Each one of us is composed of about a hundred million million, cooperating and living cells localised in specialised and different tissues. Each second of our lives we make about fifty million new cells mostly to replace ‘worn out’ cells and those that have sacrificed their life for other cells e.g. the skin’s epidermal cells. We also need to produce vast numbers of new defence cells when the body is invaded by pathogens.

What do cells need in order to work efficiently?

The local environment of a cell must be favourable. It must be at the correct concentration and pH. All the materials needed by the cell must be present in sufficient quantities. Our cells’ local environment is called tissue or extracellular fluid.

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Why are cells small?

Cell volume is a guide to the amount of cellular ‘machinery’ and metabolic activity. Materials, which sustain cell activity, can only pass in and out of cells through the surface. Therefore, the greater the surface area per unit volume, the greater the cell’s import and export efficiency.

NanoCrystal® Technology

- how volume and surface area relate

Small particles dissolve more quickly
Put a large cube of sugar into a cup of hot water and see how long it takes to dissolve. Then cut a similar cube into four smaller cubes and do the same thing. The smaller cubes dissolve more quickly because the ratio of surface area to volume is larger. As such, the small cubes expose more surface area to the solvent. This is why scientists at Elan set out to develop a process for grinding pharmaceutical substances down into very small particles which is known as nanomilling. The process is marketed by Elan Drug Technologies under the registration name of NanoCrystal® Technology and licensed to other pharmaceutical companies.

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This diagram shows a particle with a surface area of 6cm2. After nanomilling the total surface area of the smaller particles is 24cm2. However, the sum of the volumes of the 64 smaller particles is equal to the volume of the large particle. The gastrointestinal tract will enable more molecules of drug to dissolve in the biological fluids with greater transit across membrane barriers into the circulatory system.

Diagram by courtesy of the Elan Corporation plc

A discovery that required two different industries

What might the pharmaceutical industry and the photographic industry have in common that could generate a new invention, over 80 patent applications and four new commercial products since 1999. Well, it was a mutual interest in the manufacture of very small particles.

The photographic industry knew how to manufacture small particles by using nanomilling techniques. The pharmaceutical industry needed a way to reduce the size of certain pharmaceuticals so that they would dissolve more rapidly in biological fluids and so circulate more effectively in the bloodstream.

Cooperation between Kodak (the photographic industry) and Sterling Winthrop (the pharmaceutical industry) led to the original invention. A small company called NanoSystems was formed. The company was subsequently acquired by Elan.

What is blood made of?

Blood is a mixture of solids suspended in a complex solution called plasma. The suspended solids, (red and white blood cells plus platelets), make up 45% of the blood and plasma the remaining 55%.

The solvent of plasma is water. If materials are water-soluble they are carried in solution. Such materials include proteins, carbohydrates, amino acids, fatty acids, mineral nutrients and some vitamins.

Oxygen is not very soluble but it is transported in great quantity by red blood corpuscles where it is bound rather loosely to haemoglobin. This allows the oxygen to be easily ‘picked up’ and ‘released’. This form of transport allows the blood to carry seventy five times more oxygen than it could by pure solution.

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Although carbon dioxide is more soluble than oxygen, its transport is improved by converting 70% of it to a much more soluble form as bicarbonate (hydrogen-carbonate) ions. Of the remaining 30%, about 20% is carried in combination with haemoglobin in red blood cells, leaving only 10% carried in direct solution.

Very poorly water soluble or insoluble substances like lipids, cholesterol and fat-soluble vitamins are carried in loose combination with soluble proteins such as lipoproteins and albumin.

It is amazing that our blood has evolved mechanisms to transport a variety of essential materials despite their wide difference in water solubility.

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How does blood reach the cells?

The blood is kept flowing continuously through a closed system of blood vessels. Every part of our body has a dense network of microscopic blood capillaries. In fact, every tissue cell is within 0.02 mm of a blood capillary. It is at the capillaries that exchange between tissue cells and blood takes place.

How are materials exchanged at the blood capillaries?

The walls of the blood capillaries are only one cell thick. They also contain many intercellular and intracellular pores. Small soluble molecules move by diffusion through these pores but large protein molecules cannot pass through. Some larger fat-soluble molecules can dissolve their way through the cell membranes of the capillary cells.

The red blood cells and platelets are retained within the blood because they are too big to fit through the pores. White blood cells have a special technique to pass out of the blood to ‘hunt down’ pathogens in the tissues.

The higher blood pressure at the arteriole end of the capillary squeezes out a clear fluid through the capillary pores – it has a similar composition to plasma but only 2% dissolved protein. This non-stop leakage through the capillaries ensures that the local environment of the tissue cells is continuously replaced, refreshed and maintained in an ideal condition for cell metabolism.

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