Vaccinations May Become Needle-Free with Novel Oral Delivery System

Needleless, pill-sized vaccines may one day become a reality, according to a proof-of-concept study published inScience Translational Medicine.

The study demonstrated that the technology MucoJet can deliver vaccine-sized molecules to immune cells in the mouths of animals, bringing society one step closer to improved oral vaccine delivery.

The MucoJet is placed against the inside of an individual’s cheek and releases a jet stream that directly targets the buccal region. The mouth’s buccal region has an abundance of immune cells and is an area where many infections enter the body.

Penetrating the thick mucosal layer in this part of the oral cavity has proven to be a challenge with existing technology, such as oral spray used forinfluenza vaccination.

The results of the study showed that the MucoJet could deliver a high-pressure stream of liquid and immune system-triggering molecules that penetrate the mucosal layer to stimulate an immune response in the buccal region.

Although the jet of the self-administered device is pressurized, the authors said it is not uncomfortable and would remove the sting of needles. “This jet is similar in pressure to a water pick that dentists use,” said Kiana Aran, who developed the technology.

The portable technology stores vaccines in powder form and could one day delivery vaccines to remote locations, but years of further research is needed before the device would become commercially available.

The following are the specs of the MucoJet:

1. 15 X 7 mm cylindrical 2-compartment plastic device

2. Solid components are 3D-printed from an inexpensive biocompatible and water-resistant plastic resin

3. Exterior department holds 250 ml of water

a. Vaccine reservoir contains a 100-ml chamber of vaccine solution with a piston at one end and a sealed 200-m diameter delivery nozzle at the other end

b. Propellant reservoir contains the dry chemical propellant citric acid and sodium bicarbonate. It’s separated from the vaccine reservoir at one end by the built-in porous membrane and movable piston, and is sealed at the other end from the exterior compartment with a dissolvable membrane

4. Interior compartment is composed of 2 reservoirs separated by a porous plastic membrane and movable piston.

To administer the MucoJet, a patient clicks together the interior and exterior compartments. The membrane then dissolves, the water contacts the chemical propellant, and the ensuing chemical generates carbon dioxide gas. The gas increases the pressure in the propellant chamber, causing the piston to move, ensuring uniform movement of the ejected drug and blocks the exit of fizz from the carbon dioxide through the nozzle. One the pressure in the propellant chamber is high enough, the force on the piston breaks the nozzle seal of the vaccine reservoir. The vaccine solution is then ejected from the device’s nozzle and penetrates the mucosal layer of the buccal tissue to deliver the vaccine to antigen-presenting cells.

For a laboratory experiment in plastic dishes using mucosal layers and buccal tissues from pigs, the investigators tested the MucoJet’s ability to deliver the immune stimulating protein ovalbumin, across the mucosal layer.

The results of the experiment showed an 8-fold increase in the delivery of ovalbumin over the course of 3 hours compared with a control experiment of administering ovalbumin with a dropper.

Next, the investigators tested different pressures of the vaccine jet and found that increasing the output pressure increased the delivery of ovalbumin to the tissue. The findings indicate that delivery efficacy improves with increased pressure.

“The pressure is very focused, the diameter of the jet is very small, so that’s how it penetrates the mucosal layer,” Aran said.

The ability of the MucoJet to deliver ovalbumin to buccal tissue in rabbits was also tested. The results showed a 7-fold increase in delivery of the ovalbumin compared with control experiments with droppers.

In animals administered ovalbumin by the MucoJet, the investigators found key antibodies in their blood that were 3 orders of magnitude higher than in the blood from rabbits treated with ovalbumin by a dropper.

Although the study did not compare the MucoJet to vaccine delivery with a needle, data suggest the MucoJet can trigger an immune response that is as good as or better than delivery with a needle, especially for mucosal pathogens.

The investigators hope the MucoJet will be available in 5 to 10 years, but the next step is to test the delivery of real vaccine in larger animals. Furthermore, they hope to engineer a MucoJet version that can be swallowed and release vaccine internally.

Currently, investigators are considering different designs, shapes, and sizes to simplify vaccine administration procedures and increase patient compliance, especially for children.

“Imagine if we could put the MucoJet in a lollipop and have kids hold it in their cheek,” Aran said. “They wouldn’t have to go to a clinic to get a vaccine.”