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How to deliver the bacteria in the intestine?

The gelatine-based composition of the capsule dissolves at neutral pH to deliver its payload to the duodenum. Right after the dissolution of the gelatine capsule, the HPMC swells to form a viscuous obstruction. This process creates an environment in the jejunum where bacteria can statically proliferate. Thus, HPMC, beside its properties as a diluent, is also called a bio-adhesive for its ability to stick to the membranes of the intestins and form an obstruction.

How to prove the real efficiency of our capsule?

As a proof of concept, we fulfilled the two basic requirements of the European Pharmacopeia to make a gastro-enteric resistant capsule which are as follows:

1. No dissolution of the capsule after 2 hours of exposure to gastric acid (solution at pH = 2)
2. Dissolution of the capsule within 1 hour of exposure to water (Phosphate Buffer solution, pH = 7) right afterwards

The dissolution machine lifts raises and lowers a basket into a 800mL beaker (Figure 9). In each experiment, we were able to test 6 capsules spread into 6 separate columns (Figure 10). These columns can be sealed on top with a lid to increase the dissolution and mimic different segments of the intestines.

We observed that the capsules maintained their integrity after one hour of exposure to gastric acidity (Figure 11) and didn't release their contents into solution (Figure 12).

We continued the experiment for an additional hour to confirm that even after two hours of exposure to a pH=2 solutes, the capsules were still not dissolved (Figure 13) and hadn't released their contents (Figure 14).

The acid solution was clear after removing the capsules (Figure 15), showing that the first condition of the European Pharmacopeoa to create a gastro-enteric resistant capsule has been fullfilled.

The capsules were fully intact when they were transferred to a PBS (Figure 16) and none of the contents were immediately released (Figure 17).

The capsules began to dissolve after 15 minutes in PBS buffer (Figure 18) and the dye solution began to be released (Figure 19).

The capsules continue to dissolve after 30 minutes in PBS buffer (Figure 20) and released their contents (Figure 21).

The capsules continue to dissolve after 40 minutes in PBS buffer (Figure 22) and release their contents (Figure 23).

The capsules continue to dissolve after 50 minutes in PBS buffer (Figure 24) and release their contents (Figure 25).

The capsules were fully dissolved after 60 minutes in PBS (Figure 26) and had released their contents into the PBS solution (Figure 27).

Conclusion and perspectives

Our polymeric capsule successfully bypassed stomach acidity (pH=2) and rapidly dissolved to release its contents at neutral pH as in the duodenum and jejunum. The capsule thus fulfills the requirements of the European Pharmacopeia.

The purpose of this capsule is to impact such a treatment could have on the health system. Blood-lettings are expensive and this treatment can be seen as an alternative or a complement to blood-lettings.

The next step for the capsule project is to mix the colloidal silica and hydroxypropylmethylcellulose with a concentrated culture of our siderophore-overexpressing Iron Coli. After encapsulating them in gelatine and methacrylic acid, we must establish that our bacteria can be released from the capsule and survive. If these tests are conclusive it could be possible to test the capsule in hemochromatosis mice.

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