One Vaccine Injection Could Carry Many Doses

Library of Tiny/Encased Vaccine Particles

 
An innovative 3-D fabrication system has been designed by the MIT engineers that tend to generate a novel kind of drug-carrying particle enabling various doses of a drug or vaccines to be provided over an extended time period with only an injection.

 The innovative micro particles are said to be made of biocompatible, FDA approved polymer that can be considered to degrade at specific times, spilling out the contents of the `cup’. Robert Langer, the David H Koch Institute Professor at MIT had commented that they are excited regarding this work since for the first time they can create a library of tiny, encased vaccines particles wherein each are programmed to release at an accurate, predictable time in order that individuals could probably receive a single injection which in effect would tend to have several boosters that are built in it already.

This could have a substantial influence on the victims everywhere particularly in the developing world where the person’s compliance seems to be at the lowest. A research scientist at MIT’s Koch Institute for Integrative Cancer Research, Ana Jaklenec and Langer are the senior authors of the paper which appeared online in Science on Sept 14.
 

Several Doses of Vaccines/One Injection

 
The lead authors of the paper are postdoc Kevin McHugh and earlier postdoc Thanh D. Nguyen presently an assistant professor of mechanical engineering at the University of Connecticut. As part of a project subsidized by the Bill and Melinda Gates Foundation, Langer’s lab started working on the innovative drug delivery particles that was looking for means of delivering several doses of vaccines over specified period to time with only one injection.

This would enable babies in developing nations who may not see a doctor often to get one injection after birth which would deliver all of the vaccines they would need during the first one or two years of life. Langer had earlier developed polymer particles with drugs implanted all over the particle enabling them to be gradually released over a period of time. But the researchers needed to come up with a way to deliver short burst of a drug at particular intervals, for the project to mimic the manner in which a series of vaccines could be administered.
 

PLGA – Biocompatible Polymer

 
In order to accomplish their goal on drug or vaccines, they started to cultivate a sealable polymer cup made from PLGA that is a biocompatible polymer which had been already approved for usage in medical devices like the implants, sutures as well as prosthetic devices.

It is said that PLGA could also be intended in degrading at various rates enabling for fabrication of numerous particles which tend to release their contents at various times. Conservative 3-D printing techniques is said to incompatible for the material as well as the dimension which the researchers needed and hence they had to create a new method of fabricating the cups gaining inspiration from computer chip manufacturing.

They developed silicon molds for the cups as well as the lids utilising the photolithography. Huge selections of around 2,000 molds are placed on a glass slide wherein these are utilised in shaping the PLGA cups (cups with edge lengths of some hundred microns) and lids. The researchers had engaged a custom-built, automated dispensing method of filling each cup and the system was heated slightly till the cup and lid fused together, sealing the drug within, when the selection of polymer cups had been shaped.
 

StampED Assembly of Polymer Layers

 
Jaklenec had stated that every layer is fabricated at first on its own and thereafter assembled together. Part of the novelty is really in how they align and seal the layers. By doing so they developed a new system which could make structures that current 3-D printing methods are unable to do. The latest system is known as SEAL – StampED Assembly of polymer Layers, and can be utilised with any thermoplastic material enabling fabrication of microstructures with complex geometries that tend to have broad application comprising of injectable pulsatile drug delivery, pH sensors together with 3-D microfluidic devices.

An assistant professor of mechanical engineering and biomedical engineering at Vanderbilt University, Leon Bellan stated that the approach tends to provide an impressive amount of control in constructing 3-D micro particles. Bellan who had not been involved in the study stated that it seems to be a new take on 3-D printing procedure as well as an elegant solution in building macroscopic 3-D structures out of material which are relevant for biomedical application.

The molecular weight of the PLGA polymer together with the backbone structure of the polymer molecule tends to regulate how quick the particles could degrade after the vaccines. The rate of degradation determines when the drug would be released and on injecting several particles which degrade at varied rates, the researcher could create a strong burst of drug or vaccines at predetermined time point.
 

Vaccines in One Shot

 
McHugh had stated that in the developing world that could be the variance between not getting vaccinated and receiving all of the vaccines in one shot. The researchers showed that in mice, particle release in sharp bursts without previous leakage was at 9, 20 and 41 days after the injection. Thereafter they examined particles that were filled with ovalbumin, which is a protein that is found in egg whites and is generally utilised to experimentally motivate an immune response.

Utilising a mixture of particles which tend to release ovalbumin at 9 and 41 day after injection they discovered that a particular injection of these particles had the capabilities of inducing a strong immune response which was equivalent to that triggered by two conservative injections with twice the dose. Besides this, the researchers also designed particles which could degrade as well as release hundreds of days after the injection.

 The researcher state that one experiment of developing long-term vaccine based on these particles is of ensuring that the encapsulated drug or vaccines tends to be stable at body temperature for a long time before being released. They now intend to test these delivery particles with various drugs comprising of prevailing vaccines like inactivated polio vaccine together with fresh vaccines which are in the development stage. Moreover they are also working on plans of stabilizing the vaccines.

The researchers have also designed particles that can degrade and release hundreds of days after injection. One challenge to developing long-term vaccines based on such particles, the researchers say, is making sure that the encapsulated drug or vaccine remains stable at body temperature for a long period before being released. They are now testing these delivery particles with a variety of drugs, including existing vaccines, such as inactivated polio vaccine, and new vaccines still in development. They are also working on strategies to stabilize the vaccines.

“The SEAL technique could provide a new platform that can create nearly any tiny, fillable object with nearly any material, which could provide unprecedented opportunities in manufacturing in medicine and other areas,” Langer says. These particles could also be useful for delivering drugs that have to be given on a regular basis, such as allergy shots, to minimize the number of injections.

Other authors on the paper are Allison Linehan, David Yang, Adam Behrens, Sviatlana Rose, Zachary Tochka, Stephanie Tzeng, James Norman, Aaron Anselmo, Xian Xu, Stephanie Tomasic, Matthew Taylor, Jennifer Lu, and Rohiverth Guarecuco.