Fate of gel bleed

1. Introduction
Silicone polymers contain a range of different sizes of silicone molecules ranging from small amounts of the compounds used to make the polymer (low molecular weight silicones) to a variety of sizes of polymer chain (with molecular weights from 7000 upwards, average 30000). The precise composition of a silicone varies with its intended physical properties. The typical levels for the individual low molecular weight silicones in breast implant gel are 800-1500 ppm (i.e. 80-150 mg/100 g). These low molecular weight silicones have a number of other uses including hair care products, skin care products, antiperspirants and deodorants.

The absorption and distribution of these low molecular weight silicones, like all small molecules, is determined by their solubilities in water and fat. The water solubility is important for transport to and from cell membranes and the fat solubility determines the transport into cell membranes. As its weight increases the size and shape of the molecule become far more important influences in the ability to absorb and distribute compounds. For the largest molecules absorption and distribution rely on the specialised mechanisms evolved to handle small amounts of naturally occurring macromolecules.

2. Absorption and distribution
Transport of a molecule requires it to go into solution to reach the cell membrane, pass through the lipid cell membrane and go into solution to leave the cell membrane. All of these processes are controlled by the physicochemical properties of the molecule and governed by fundamental laws such as Fick's law. The cohesion of a membrane barrier is determined by the tightness of intercellular junctions.

Three factors influence the distribution (movement) of molecules in the body solubility, lipophilicity and molecular size/shape. For small molecules (up to 500-600 Da) the last can be ignored, whereas for medium molecules (600-1500 Da) the interplay of all three properties is critical. The molecular size/shape is the most important factor for large synthetic molecules. These molecules are mainly transported by specialised mechanisms e.g. following engulfment by cells.

3. Metabolism and excretion
In order to excrete small molecules it is desirable to increase their hydrophilicity and/or size. This is the main function of foreign compound metabolism. Phase 1 reactions increase the hydrophilicity e.g. by hydroxylation whilst phase 2 conjugation reactions increase molecular weight. These reactions are performed by enzymes within the cell.
The distribution of silicone and its precursors is governed by the same processes. The silicone polymer (PDMS) is a large crosslinked molecule hydrophobic molecule that is essentially insoluble. The distribution of silicone polymer is essentially restricted to phagocytosis. The short chain linear and cyclic precursors have been demonstrated to absorb, distribute, metabolise and excrete in relation to their solubility, molecular weight and lipophilicity. As their molecular weight increases their solubility and oral absorption decrease, essentially reaching zero at more than 8 siloxy units.

For those short chain molecules where half lives were measured these were in the order of hours to days. The metabolism of the short chain precursors has been studied demethylation reactions have been shown to occur. However in no case has the loss of more than two methyl substituents been shown, there is no metabolism to silicates. There is no evidence of demethylation of silicone polymer, this probably reflects its inability to cross cell membranes and fit into enzyme active sites.