One injection, many doses

Materials World magazine
,
1 Nov 2017

A new 3D fabrication method could allow polymer microparticles to administer multiple drug doses from just one injection. 

Engineers from Massachusetts Institute of Technology (MIT), USA, have developed a new 3D fabrication method – StampEd Assembly of polymer Layers (SEAL) – that can create drug-carrying microstructures. Made from biocompatible and Food and Drug Administration-approved poly (lactic-co-glycolic acid, PLGA), the microstructures could administer multiple doses of a vaccine over a period of time with just one injection. A syringe and needle would be used to administer them. 

The microstructures have internal spaces, which can be filled with a solid or liquid, and sealed. The PLGA container can be designed to degrade at particular times, releasing its contents.  

This burst of the drug/vaccine is achieved by injecting groups of particles that degrade at different rates. The time at which the microstructures degrade is determined by the structure and molecular weight of the PLGA polymer. 

Tested on mice, the researchers found that the particles degraded, releasing their contents, nine, 20 and 41 days after injection. Particles that degrade hundreds of days after injection were also designed. 

Robert Langer, MIT David H Koch Institute Professor and senior author on the paper Fabrication of fillable microparticles and other complex 3D microstructures, published in Science, commented, ‘This could have a significant impact on patients everywhere, especially in the developing world where patient compliance is particularly poor.’

Previously, Langer has developed polymer particles embedded with drugs that are released steadily over a time period. But, the MIT team wanted to replicate how vaccines and boosters are administered, developing a way in which bursts of the drug could be released at particular times. 

As existing 3D printing techniques were unsuitable for this project’s material and size requirements, the team developed SEAL. Current high-resolution 3D printing requires ultraviolet curable materials that contain some additives that may not be safe within the human body, as well as not being compatible with biomedical materials such as PLGA, according to Ana Jaklenec, a research scientist at MIT’s Koch Institute for Integrative Cancer Research and a senior author on the paper. 

About 2,000 silicon moulds were used to shape the PLGA into cubes and separate lids, measuring a few hundred micrometres. Jaklenec explains this method. ‘We have developed a bottom-up, high-resolution microstructure fabrication technique to create microdevices with complex geometries. Two or more silicon moulds with complementary patterns are etched using standard microfabrication techniques. Polydimethylsiloxane (PDMS) is then cured on the surface of each silicon wafer to produce inverse elastomeric moulds.’

After this, the PDMS moulds are filled with a heated polymer. ‘The first layer is then delaminated onto a separate surface, such as glass, using heat-assisted microtransfer moulding,’ said Jaklenec. ‘Subsequent layers of the final structure are then assembled using a layer-by-layer sintering process under microscopic alignment to produce a large array of microstructures. This process draws on elements from existing technology, including laminated object manufacturing, microfabrication-based surface patterning and thermal bonding of PLGA, to create discrete polymeric microdevices with well-defined geometry.’

The particles are currently being tested using existing vaccines, including inactivated polio vaccine, and those still in development. The team is working with pharmaceutical companies and investors to scale-up and develop manufacturing methods for the technology. Jaklenec added, ‘Our goal is to have them stored dry so they are easier to transport, especially in the developing world.’

However, the researchers are still working on the issue of keeping the drug or vaccine stable inside the body for a long period of time. The team claims the particles cause only a minimal foreign body reaction similar to potential reactions to currently used injected vaccines, which range from redness and swelling at the injection site to fever.

To read the paper in full, visit bit.ly/2f4rbrD