Phagocytosis of spherical and ellipsoidal micronetwork colloids from crosslinked poly(epsilon-caprolactone)
- The effect of non-spherical particle shapes on cellular uptake has been reported as a general design parameter to control cellular recognition of particulate drug carriers. Beside shape, also size and cell-particle ratio should mutually effect phagocytosis. Here, the capability to control cellular uptake of poly(epsilon-caprolactone) (PCL) based polymer micronetwork colloids (MNC), a carrier system that can be transferred to various shapes, is explored in vitro at test conditions allowing multiple cell-particle contacts. PCL-based MNC were synthesized as spheres with a diameter of similar to 6, similar to 10, and 13 mu m, loaded with a fluorescent dye by a specific technique of swelling, redispersion and drying, and transferred into different ellipsoidal shapes by a phantom stretching method. The boundaries of MNC deformability to prolate ellipsoid target shapes were systematically analyzed and found to be at an aspect ratio AR of similar to 4 as obtained by a phantom elongation epsilon(ph) of similar to 150%. Uptake studies with aThe effect of non-spherical particle shapes on cellular uptake has been reported as a general design parameter to control cellular recognition of particulate drug carriers. Beside shape, also size and cell-particle ratio should mutually effect phagocytosis. Here, the capability to control cellular uptake of poly(epsilon-caprolactone) (PCL) based polymer micronetwork colloids (MNC), a carrier system that can be transferred to various shapes, is explored in vitro at test conditions allowing multiple cell-particle contacts. PCL-based MNC were synthesized as spheres with a diameter of similar to 6, similar to 10, and 13 mu m, loaded with a fluorescent dye by a specific technique of swelling, redispersion and drying, and transferred into different ellipsoidal shapes by a phantom stretching method. The boundaries of MNC deformability to prolate ellipsoid target shapes were systematically analyzed and found to be at an aspect ratio AR of similar to 4 as obtained by a phantom elongation epsilon(ph) of similar to 150%. Uptake studies with a murine macrophages cell line showed shape dependency of phagocytosis for selected conditions when varying particle sizes (similar to 6 and 10 mu m),and shapes (epsilon(ph): 0, 75 or 150%), cell-particle ratios (1:1, 1:2, 1:10, 1:50), and time points (1-24 h). For larger-sized MNC, there was no significant shape effect on phagocytosis as these particles may associate with more than one cell, thus increasing the possibility of phagocytosis by any of these cells. Accordingly, controlling shape effects on phagocytosis for carriers made from degradable polymers relevant for medical applications requires considering further parameters besides shape, such as kinetic aspects of the exposure and uptake by cells.…
Author details: | Fabian FriessGND, Toralf RochORCiD, Barbara Seifert, Andreas LendleinORCiDGND, Christian WischkeORCiDGND |
---|---|
DOI: | https://doi.org/10.1016/j.ijpharm.2019.118461 |
ISSN: | 0378-5173 |
ISSN: | 1873-3476 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/31247276 |
Title of parent work (English): | International Journal of Pharmaceutics |
Publisher: | Elsevier |
Place of publishing: | Amsterdam |
Publication type: | Article |
Language: | English |
Year of first publication: | 2019 |
Publication year: | 2019 |
Release date: | 2020/11/30 |
Tag: | Macrophage; Particle shape; Phagocytosis; Poly(epsilon-caprolactone); Polymer micronetwork colloids |
Volume: | 567 |
Number of pages: | 7 |
Funding institution: | Helmholtz-AssociationHelmholtz Association |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Chemie |
DDC classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
Peer review: | Referiert |