Engineering Biocoatings to Prolong Drug Release from Supraparticles

Yutian Ma, Christina Cortez-Jugo, Jianhua Li, Zhixing Lin, Rachael T. Richardson, Yiyuan Han, Jiajing Zhou, Mattias Björnmalm, Orlagh M. Feeney, Qi Zhi Zhong, Christopher J.H. Porter, Andrew K. Wise, Frank Caruso

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Supraparticles (SPs) assembled from smaller colloidal nanoparticles can serve as depots of therapeutic compounds and are of interest for long-term, sustained drug release in biomedical applications. However, a key challenge to achieving temporal control of drug release from SPs is the occurrence of an initial rapid release of the loaded drug (i.e., "burst" release) that limits sustained release and potentially causes burst release-associated drug toxicity. Herein, a biocoating strategy is presented for silica-SPs (Si-SPs) to reduce the extent of burst release of the loaded model protein lysozyme. Specifically, Si-SPs were coated with a fibrin film, formed by enzymatic conversion of fibrinogen into fibrin. The fibrin-coated Si-SPs, FSi-SPs, which could be loaded with 7.9 ± 0.9 μg of lysozyme per SP, released >60% of cargo protein over a considerably longer period of time of >20 days when compared with the uncoated Si-SPs that released the same amount of the cargo protein, however, within the first 3 days. Neurotrophins that support the survival and differentiation of neurons could also be loaded at ∼7.3 μg per SP, with fibrin coating also delaying neurotrophin release (only 10% of cargo released over 21 days compared with 60% from Si-SPs). In addition, the effects of incorporating a hydrogel-based system for surgical delivery and the opportunity to control drug release kinetics were investigated - an alginate-based hydrogel scaffold was used to encapsulate FSi-SPs. The introduction of the hydrogel further extended the initial release of the encapsulated lysozyme to ∼40 days (for the same amount of cargo released). The results demonstrate the increasing versatility of the SP drug delivery platform, combining large loading capacity with sustained drug release, that is tailorable using different modes of controlled delivery approaches.

Original languageEnglish
Pages (from-to)3425-3434
Number of pages10
JournalBiomacromolecules
Volume20
Issue number9
DOIs
Publication statusPublished - 1 Jan 2019

Cite this

Ma, Y., Cortez-Jugo, C., Li, J., Lin, Z., Richardson, R. T., Han, Y., Zhou, J., Björnmalm, M., Feeney, O. M., Zhong, Q. Z., Porter, C. J. H., Wise, A. K., & Caruso, F. (2019). Engineering Biocoatings to Prolong Drug Release from Supraparticles. Biomacromolecules, 20(9), 3425-3434. https://doi.org/10.1021/acs.biomac.9b00710