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Team:Imperial College London/Manufacturing Considerations
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| - | = | + | =Manufacturing Considerations= |
| - | Pill manufacture is not only concerned with drug release but also by synthesis, purification, packaging, storage, administration and quality control. <i>The E.ncapsulator</i> has been designed to address each of these important manufacturing considerations. | + | Pill manufacture is not only concerned with drug release but also by synthesis, purification, packaging, storage, administration and quality control. <b><i>The E.ncapsulator</i></b> has been designed to address each of these important manufacturing considerations. By taking these considerations into account, we hope to present <b><i>The E.ncapsulator</i></b> as a viable, cost-effective alternative to current drug production and delivery methods. |
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If <i>The E.ncapsulator</i> is to be adopted as a drug delivery platform, it must be able to synthesise any polypeptide. To this end, we have designed a 'universal adaptor' such that peptides which do not begin with the amino acid methionine can be synthesised. In addition, we have 'codon optimised' all non native <i>E.coli</i> genes to maximise gene expression efficiency. | If <i>The E.ncapsulator</i> is to be adopted as a drug delivery platform, it must be able to synthesise any polypeptide. To this end, we have designed a 'universal adaptor' such that peptides which do not begin with the amino acid methionine can be synthesised. In addition, we have 'codon optimised' all non native <i>E.coli</i> genes to maximise gene expression efficiency. | ||
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| - | In <b><i>The E.ncapsulator</i></b>, polypeptide synthesis (<b>Module 1</b>) and | + | In <b><i>The E.ncapsulator</i></b>, polypeptide synthesis (<b>Module 1</b>) and encapsulation of the cells(<b>Module 2</b>) occur in the same place. This duel production and delivery platform means that there is no need for expensive downstream purification processes. <br><br> |
| + | As <i>The E.ncapsulator</i> is designed to be safe to consume, purification of the drug is not necessary. This means that our solution represents a cost-effective alternative to current production methods. | ||
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| - | Storage has been considered in two ways. Firstly trehalose facilitates freeze drying and secondly we have been experimenting with a number if secondary encapsulation technologies including: xantham gum, milk protein and gelatin. Trehalose is a naturally occuring sugar which is | + | Storage has been considered in two ways. Firstly trehalose facilitates freeze drying and secondly we have been experimenting with a number if secondary encapsulation technologies including: xantham gum, milk protein and gelatin. <br><br><br>Trehalose is a naturally occuring sugar which is known to be important in resistance to dessication and temperature shock by many bacterial species. We have included several genes coding for the enzymes responsible for the conversion of glucose to trehalose. Secondary encapsulation is further processing that can be performed to allow for pill manufacture. |
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| - | + | The encapsulation of the cell with the colanic acid coat facilitates transport of <b><i>The E.ncapsulator</i></b> through the stomach, and protecting the contents against acid breakdown. Furthermore, we have experimented with different secondary capsules that are edible and cheap to produce. This post-processing means transport and dose control of the product is much easier. | |
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Since we are depending on a population of cells to produce a biologically active polypeptide our bets are hedged. In that if one cell fails to produce any protein it will have a minimal impact on the whole system. | Since we are depending on a population of cells to produce a biologically active polypeptide our bets are hedged. In that if one cell fails to produce any protein it will have a minimal impact on the whole system. | ||
| - | Another important aspect of quality control is safety. To minimise risks associated with our product, we have chosen a GRAS chassis. In addition, <i>The E.ncapsulator</i>'s DNA is deleted prior to ingestion (<b>Module 3</b>). This will protect against the risks of horizontal gene transfer and colonisation. | + | Another important aspect of quality control is safety. To minimise risks associated with our product, we have chosen a GRAS (generally recognised as safe) chassis. In addition, <i>The E.ncapsulator</i>'s DNA is deleted prior to ingestion (<b>Module 3</b>). This will protect against the risks of horizontal gene transfer and colonisation. |
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Latest revision as of 12:13, 15 October 2009
Manufacturing Considerations
Pill manufacture is not only concerned with drug release but also by synthesis, purification, packaging, storage, administration and quality control. The E.ncapsulator has been designed to address each of these important manufacturing considerations. By taking these considerations into account, we hope to present The E.ncapsulator as a viable, cost-effective alternative to current drug production and delivery methods.
If The E.ncapsulator is to be adopted as a drug delivery platform, it must be able to synthesise any polypeptide. To this end, we have designed a 'universal adaptor' such that peptides which do not begin with the amino acid methionine can be synthesised. In addition, we have 'codon optimised' all non native E.coli genes to maximise gene expression efficiency.
In The E.ncapsulator, polypeptide synthesis (Module 1) and encapsulation of the cells(Module 2) occur in the same place. This duel production and delivery platform means that there is no need for expensive downstream purification processes.
As The E.ncapsulator is designed to be safe to consume, purification of the drug is not necessary. This means that our solution represents a cost-effective alternative to current production methods.
Storage has been considered in two ways. Firstly trehalose facilitates freeze drying and secondly we have been experimenting with a number if secondary encapsulation technologies including: xantham gum, milk protein and gelatin.
Trehalose is a naturally occuring sugar which is known to be important in resistance to dessication and temperature shock by many bacterial species. We have included several genes coding for the enzymes responsible for the conversion of glucose to trehalose. Secondary encapsulation is further processing that can be performed to allow for pill manufacture.
The encapsulation of the cell with the colanic acid coat facilitates transport of The E.ncapsulator through the stomach, and protecting the contents against acid breakdown. Furthermore, we have experimented with different secondary capsules that are edible and cheap to produce. This post-processing means transport and dose control of the product is much easier.
Since we are depending on a population of cells to produce a biologically active polypeptide our bets are hedged. In that if one cell fails to produce any protein it will have a minimal impact on the whole system.
Another important aspect of quality control is safety. To minimise risks associated with our product, we have chosen a GRAS (generally recognised as safe) chassis. In addition, The E.ncapsulator's DNA is deleted prior to ingestion (Module 3). This will protect against the risks of horizontal gene transfer and colonisation.
