Microfluidic Fabrication of Monodisperse Biocompatible and Biodegradable Polymersomes with Controlled Permeability
Original entry by Bryan Weinstein, Fall 2012
Authors: Shum, H. C., Kim, J.-W., & Weitz, D. A.
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.
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. Polymersomes are thus an excellent candidate to transport small amounts of material.
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 PEG is to create it from a "W/O/W double emulsion." The double emulsion then transforms into a polymersome via dewetting (for more details, look at the paper; it is rather complicated). 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).
Ultimately, a stable PEG vesicle is formed. Eventually, however, the materials the vesicle is containing should be delivered. 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, the shock 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.
 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