Microfluidic Fabrication of Monodisperse Biocompatible and Biodegradable Polymersomes with Controlled Permeability

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Original entry by Bryan Weinstein, Fall 2012

General Information

Authors: Shum, H. C., Kim, J.-W., & Weitz, D. A.

Keywords: Emulsion, Vesicle, Encapsulation, Transport, Osmotic Pressure, Membrane, Polymersome, Dewetting, Biocompatible

Summary

Encapsulation and delivery of small amounts of materials such as drugs and fragrances are important to many industries (i.e. pharmaceutical and cosmetic). Encapsulating structures should capture the appropriate material as cost-effectively as possible and should easily be triggered to release the material.

In nature, vesicles naturally encapsulate and release materials. The membrane of a vesicle is created by "amphiphilic molecules" (phospholipids) via self-assembly. Unfortunately, the membrane generally only has a thickness on the order of nanometers, resulting in poor rigidity and a "high water permeation rate" resulting in a short lifetime. Vesicles are thus not ideal candidates to transport materials.

The PEG vesicle dewetting from the double emulsion. The scale bar is 10µm.

However, synthetic vesicles have been manufactured with amphiphiles of diblock copolymers, or "polymersomes," which have thicker membranes. These vesicles have much better mechanical stability and thus much longer lifetimes. Polymersome vesicles are thus an excellent method to transport small amounts of material.

Rupturing a vesicle by utilizing osmotic pressure. The scale bar is 10µm.

The first part of this paper focuses on a microfluidic method to fabricate "PEG-PLA" polymersomes that encapsulate hydrophilic solutes. PEG is a particularly useful polymersome because it is biocompatible; it is not toxic to the human body. The first step necessary to create the vesicles is to create a "W/O/W double emulsion" stabilized by PEG. Eventually, the PEG dewets from the emulsion, forming a vesicle. The final shape of PEG vesicle is determined by the relative surface energies of the materials in the system as it is forming. If the interface between the inside of the vesicle and the external material has a larger surface energy than that between the core and membrane (shell), the membrane will wet the core, forming a stable structure. If the opposite is true, the core and membrane will separate in order to avoid wetting; this will result in an unstable structure. While the vesicle forms, it encapsulates desired material in the surrounding system (there must be a surplus of this material and it must want to attach to the vesicle).

After dewetting, a stable PEG vesicle is formed; it now needs to deliver the material it contains. One method to do this is to utilize an "Osmotic Shock." Water molecules can diffuse into and out of the vesicle; larger molecules cannot. Due to osmotic pressure, water diffuses from regions with low salt concentration to regions with high salt concentration. If an osmotic pressure change is large, it can break the vesicle.

Therefore, to rupture the vesicle, one can evaporate water in a salt-water solution, increasing the concentration of the salt outside the vesicle. Water is therefore squeezed out of the vesicle, eventually breaking it. One can also dilute the bulk phase surrounding the PEG. As the concentration of the salt will be higher inside the vesicle, water will diffuse out of it, eventually rupturing it. Weitz's paper asserts that this "simple triggered release mechanism makes [his] polymersomes a promising candidate for encapsulation and release of actives."

The properties of these vesicles can be tuned by slightly altering the PEG's properties. For example, one can change the "block ratios" of the block copolymer or the homopolymer. This will allow the membrane thickness, mechanical response, thermal stability, and many other properties to be finely controlled. This obviously has various industrial applications.

Discussion

This paper was honestly a little hard to read. I think that the authors did not include enough detail about a couple of important points. For example, there was not a discussion of how the material the vesicle encapsulates actually gets inside the vesicle. It is possible that I missed this in the text; there was a lot of chemistry that I found difficult to digest. After reading this paper twice, however, I still did not find the information; I feel like it should have been discussed more clearly. In addition, the explanation of how to form the vesicles was obtuse. Instead of relating to simple conceptual explanations, the authors seemed to layer each explanation in paragraphs and paragraphs of experimental detail. I do not think that this is (in general) an effective way to make a scientific point.

Regardless, I believe that Dr. Weitz has developed an excellent method to deliver materials to target locations via vesicles. This work has many industrial applications (as discussed above); I wonder if Weitz will seek a patent or try to capitalize on this research. Regardless, the economic viability of this method will ultimately determine its success in industry.

References

[1] Shum, H. C., Kim, J.-W., & Weitz, D. A. (2008). Microfluidic fabrication of monodisperse biocompatible and biodegradable polymersomes with controlled permeability. Journal of the American Chemical Society, 130(29), 9543-9. doi:10.1021/ja802157y