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bioRxiv · 10.1101/802801

Affinity-based polymers provide long-term immunotherapeutic drug delivery across particle size ranges optimal for macrophage targeting

Rohner, N. A.·Purdue, L.·von Recum, H. A.
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Abstract

Long term drug delivery to specific arms of the immune system can be technically challenging to provide limited off-target toxicity as well as prolonged delivery and specific cellular targeting given the limits of current drug delivery systems. In this work, we demonstrate the robustness of a cyclodextrin (CD) polymer platform that can extend immunomodulatory drug delivery via affinity interactions to promote long-term, sustained release at multiple size scales. The parameter space of synthesis variables (pre-incubation and stirring speed) and post-synthesis grinding effects on resulting particle diameter were characterized. We demonstrate that polymerized CD forms exhibit size-independent release profiles of the small molecule drug lenalidomide (LND) and can provide similar drug delivery profiles as macro-scale CD polymer disks. CD polymer microparticles and nanoparticles demonstrated no significant cytotoxicity as compared to the base CD macromonomer when co-incubated with fibroblasts. Uptake of ground CD nanoparticles was significantly higher following incubation with RAW 264.7 macrophages in culture over originally synthesized, larger CD microparticles. Thus, the affinity/structure properties afforded by polymerized CD allow particle size to be modified to affect cellular uptake profiles independently of drug release rate for applications in cell-targeted drug delivery.

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Rohner, N. A., Purdue, L., von Recum, H. A.. 2019-10-13. Affinity-based polymers provide long-term immunotherapeutic drug delivery across particle size ranges optimal for macrophage targeting. https://doi.org/10.1101/802801

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