"Distinguishing nanoparticle drug release mechanisms by asymmetric flow" by Sheyda Shakiba, Saba Shariati et al.

Faculty Publications

Title

Distinguishing nanoparticle drug release mechanisms by asymmetric flow field-flow fractionation

Authors

Sheyda Shakiba, Department of Civil & Environmental Engineering, University of Houston, Houston, TX 77004, United States.
Saba Shariati, School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, AZ 85287, United States.
Haoran Wu, Department of Civil & Environmental Engineering, University of Houston, Houston, TX 77004, United States.
Carlos E. Astete, Department of Biological & Agricultural Engineering, Louisiana State University, Baton Rouge, LA 70803, United States.
Rafael Cueto, Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, United States.
Elham H. Fini, School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, AZ 85287, United States.
Debora F. Rodrigues, Department of Civil & Environmental Engineering, University of Houston, Houston, TX 77004, United States.

Document Type

Article

Publication Date

12-1-2022

Abstract

This research demonstrates the development, application, and mechanistic value of a multi-detector asymmetric flow field-flow fractionation (AF4) approach to acquire size-resolved drug loading and release profiles from polymeric nanoparticles (NPs). AF4 was hyphenated with multiple online detectors, including dynamic and multi-angle light scattering for NP size and shape factor analysis, fluorescence for drug detection, and total organic carbon (TOC) to quantify the NPs and dissolved polymer in nanoformulations. The method was demonstrated on poly(lactic-co-glycolic acid) (PLGA) NPs loaded with coumarin 6 (C6) as a lipophilic drug surrogate. The bulk C6 release profile using AF4 was validated against conventional analysis of drug extracted from the NPs and complemented with high performance liquid chromatography - quadrupole time-of-flight (HPLC-QTOF) mass spectrometry analysis of oligomeric PLGA species. Interpretation of the bulk drug release profile was ambiguous, with several release models yielding reasonable fits. In contrast, the size-resolved release profiles from AF4 provided critical information to confidently establish the release mechanism. Specifically, the C6-loaded NPs exhibited size-independent release rate constants and no significant NP size or shape transformations, suggesting surface desorption rather than diffusion through the PLGA matrix or erosion. This conclusion was supported through comparative experimental evaluation of PLGA NPs carrying a fully entrapped drug, enrofloxacin, which showed size-dependent diffusive release, along with density functional theory (DFT) calculations indicating a higher adsorption affinity of C6 onto PLGA. In summary, the development of the size-resolved AF4 method and data analysis framework fulfills salient analytical gaps to determine drug localization and release mechanisms from nanomedicines.

Publication Source (Journal or Book title)

Journal of controlled release : official journal of the Controlled Release Society

First Page

485

Last Page

496

Recommended Citation

Shakiba, S., Shariati, S., Wu, H., Astete, C. E., Cueto, R., Fini, E. H., & Rodrigues, D. F. (2022). Distinguishing nanoparticle drug release mechanisms by asymmetric flow field-flow fractionation. Journal of controlled release : official journal of the Controlled Release Society, 352, 485-496. https://doi.org/10.1016/j.jconrel.2022.10.034

Link to Full Text

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