(590e) Needle Shaped Polymeric Particles Induce Transient Cell Membrane Permeability

Polymeric carriers offer remarkable advantages over conventional drug delivery and diagnostic methods including drug encapsulation and ease of modification of physical and surface properties. Consequently, a great deal of effort has gone into optimization of these properties to facilitate targeted drug delivery and reduce rapid clearance of carriers from the body. Size and surface chemistry of polymeric carriers have been extensively explored and more recently, shape, mechanical flexibility, surface texture and compartmentalization have also found to play an important functional role. As these novel particles become commonplace in drug delivery, their interaction with cells must be understood. Here, we study the interaction of particles of different geometry with endothelial cells. Spheres, elliptical disks and needles shaped particles of different sizes (0.5 and 1 μm) and surface chemistry (positively and negatively charged) were used for the study. Spheres and elliptical disks exhibited usual endocytic behavior with perinuclear accumulation over 24 hours. The cells looked well spread and healthy and did not undergo any morphological changes upon interaction with spheres and elliptical disks. On the other hand, incubation with needle shaped particles induced distinct morphological changes. The cells showed higher mobility over the substrate and contraction in surface area whereas some cells were lifted off from the substrate. When observed for a sufficiently long time, the cells spread again and looked healthy indicating a reversal of the changes induced. The effect decreased with a decrease in particle size and increased with a positive surface charge, however, both size and surface chemistry did not fundamentally alter the effect of needles. Toxicity assays showed that needle shaped particles induced membrane permeability without affecting the proliferation capability of cells to a significant extent indicating no noticeable toxicity. The transient membrane permeability was confirmed by intracellular penetration of a concurrently applied fluorescent marker calcein with needle shaped particles. The intentional transient disruption of cell membrane by polymeric particles of a particular shape is an interesting and novel phenomenon. Further experiments to elucidate the role of dependent parameters will enable better control over the membrane permeability which can then be utilized for specific applications, for example, intracellular delivery of drugs. The findings reported here have significant implications in developing new methods of drug delivery as well studying the toxicity of particulate matter.