Drug Delivery Could Become Smooth as Silk

Wrapping oneself up in a protective cocoon and hibernating the day away is probably an attractive idea for many people. Take your favorite media device with you, and it might even be a great way to catch up on your binge TV watching. While scientists are no strangers to the appeal of cocooning themselves from the outside world for a period, a team of investigators led by researchers at the University of Cambridge and the University of Sheffield has developed a far better use for the silk-laden encasement spun by the Bombyx mori caterpillar—on a very small scale.

Findings from the new study, published in Nature Communications in an article entitled “Silk Micrococoons for Protein Stabilisation and Molecular Encapsulation”, could potentially be used to protect sensitive molecular materials that easily degrade and lose these favorable qualities during storage or processing. Additionally, the researchers are optimistic that their new method could provide a significant technological advance in various areas, including food science, biotechnology, and medicine.

“It is a common problem in a range of areas of great practical importance to have active molecules that possess beneficial properties but are challenging to stabilize for storage,” explained co-senior study investigator Tuomas Knowles, Ph.D., a fellow of St John’s College at the University of Cambridge and co-director of the Centre for Protein Misfolding Diseases. “A conceptually simple, but powerful, solution is to put these inside tiny capsules. Such capsules are typically made from synthetic polymers, which can have some drawbacks, and we have recently been exploring the use of fully natural materials for this purpose. There is potential to replace plastics with sustainable biological materials, such as silk, for this purpose.”

In the current study, the investigators developed a novel process that mimics at the microscale the way in which silkworms spin the cocoons from which natural silk is harvested. The resulting micron-scale capsules—or micrococoons—comprise a solid and tough shell of silk nanofibrils that surround and protect a center of liquid cargo and are more than a thousand times smaller than those created by silkworms.

The researchers believe that the same technology could also be used by the biopharmaceutical industry to treat a wide range of severe and debilitating illnesses. For instance, in the current study, the research team successfully showed that silk micrococoons could increase the stability and lifetime of an antibody that acts on a protein implicated in neurodegenerative diseases. While more research needs to be done to understand the specific pharmacodynamics associated micrococoon-encased molecules, Dr. Knowles told GEN that “natural silk proteins are slowly degraded inside the body, and this is the basis for their use in surgical materials.”

The new silk production process was achieved when the research team created a tiny, artificial spinning duct that copies the natural spinning process, causing the unspun silk to form into a solid. The scientists subsequently then worked out how to control the geometry of this self-assembly to create microscopic shells.

“Silk is a fantastic example of a natural structural material,” noted lead study investigator Ulyana Shimanovich, Ph.D., a postdoctoral researcher at St John’s College. “But we had to overcome the challenge of controlling the silk to the extent that we could mold it to our designs, which are much smaller than the natural silk cocoons.”

“Silk is amazing because while it is stored as a liquid, spinning transforms it into a solid,” added co-senior study investigator Chris Holland, Ph.D., head of the natural materials group at the University of Sheffield. “This is achieved by stretching the silk proteins as they flow down a microscopic tube inside the silkworm.”

Making conventional synthetic capsules can be challenging to achieve in an environmentally friendly manner and from biodegradable and biocompatible materials. Silk is not only easier to produce, but it is also biodegradable and requires less energy to manufacture.

To explore the biological viability of the silk microcapsules, the researchers successfully tested the micrococoons with an antibody that has been developed to act on alpha-synuclein, a key protein in the molecular cascade leading to Parkinson’s disease.

“Some of the most efficacious and largest selling therapeutics are antibodies,” remarked Michele Vendruscolo, Ph.D., co-director of the Cambridge Centre of Misfolding Diseases, who was not directly involved in the current study. “However, antibodies tend to be prone to aggregation at the high concentrations needed for delivery, which means that they are often written off for use in treatments, or have to be engineered to promote stability.”

Silk micrococoons could also expand the range and shelf ife of proteins and molecules available for pharmaceutical use. Since the technology can preserve antibodies, which would otherwise degrade, in cocoons with walls that can be designed to dissolve over time, it could enable the development of new treatments for cancer, or neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases.

“By containing such antibodies in micrococoons, as we did here, we could significantly extend not just their longevity, but also the range of antibodies at our disposal,” Dr. Knowles said. “We are very excited by the possibilities of using the power of microfluidics to generate entirely new types of artificial materials from fully natural proteins.”

Additionally, when asked about the ease of commercial scale-up for the newly developed process, Dr. Knowles told GEN that “Our work was on a prototype reactor for small-volume material production in the laboratory, [but] the process is in principle scalable through parallelization.”