Monday, April 9, 2018

PLGA from PolySciTech used in development of ellipsoid-shaped/lipid-coated particles with controlled cell interaction



By typical manufacturing techniques, microparticles are simple, spherical, homogenous structures with little feature of interest. This is, effectively, the only configuration possible by conventional emulsion-type manufacturing techniques. There are a great deal of potential applications for developing microparticles which do not obey this simple shape. Recently, researchers at Johns Hopkins University used PLGA (PolyVivo AP087) from PolySciTech (www.polyscitech.com) to develop oblong-shaped microparticles with a carefully controlled coating of a lipid shell bearing various moieties. They investigated the interactions of these particles with cells and proteins and found that ellipsoid particles were resistant to macrophage uptake as well as had several other interesting features. This research holds promise for the development of advanced drug-delivery platforms as well as for other biomedical applications. Read more: Meyer, Randall A., Mohit P. Mathew, Elana Ben-Akiva, Joel C. Sunshine, Ron B. Shmueli, Qiuyin Ren, Kevin J. Yarema, and Jordan J. Green. "Anisotropic Biodegradable Lipid Coated Particles for Spatially Dynamic Protein Presentation." Acta Biomaterialia (2018). https://www.sciencedirect.com/science/article/pii/S1742706118301880

“Abstract: There has been growing interest in the use of particles coated with lipids for applications ranging from drug delivery, gene delivery, and diagnostic imaging to immunoengineering. To date, almost all particles with lipid coatings have been spherical despite emerging evidence that non-spherical shapes can provide important advantages including reduced non-specific elimination and increased target-specific binding. We combine control of core particle geometry with control of particle surface functionality by developing anisotropic, biodegradable ellipsoidal particles with lipid coatings. We demonstrate that these lipid coated ellipsoidal particles maintain advantageous properties of lipid polymer hybrid particles, such as the ability for modular protein conjugation to the particle surface using versatile bioorthogonal ligation reactions. In addition, they exhibit biomimetic membrane fluidity and demonstrate lateral diffusive properties characteristic of natural membrane proteins. These ellipsoidal particles simultaneously provide benefits of non-spherical particles in terms of stability and resistance to non-specific phagocytosis by macrophages as well as enhanced targeted binding. These biomaterials provide a novel and flexible platform for numerous biomedical applications. Statement of Significance: The research reported here documents the ability of non-spherical polymeric particles to be coated with lipids to form anisotropic biomimetic particles. In addition, we demonstrate that these lipid-coated biodegradable polymeric particles can be conjugated to a wide variety of biological molecules in a “click-like” fashion. This is of interest due to the multiple types of cellular mimicry enabled by this biomaterial based technology. These features include mimicry of the highly anisotropic shape exhibited by cells, surface presentation of membrane bound protein mimetics, and lateral diffusivity of membrane bound substrates comparable to that of a plasma membrane. This platform is demonstrated to facilitate targeted cell binding while being resistant to non-specific cellular uptake. Such a platform could allow for investigations into how physical parameters of a particle and its surface affect the interface between biomaterials and cells, as well as provide biomimetic technology platforms for drug delivery and cellular engineering. Keywords: Lipids; Polymers; Membrane fluidity; Particle shape; Biomimetic”

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