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Biomacromolecules. 2019 Sep 9;20(9):3425-3434. doi: 10.1021/acs.biomac.9b00710. Epub 2019 Aug 14.

Engineering Biocoatings To Prolong Drug Release from Supraparticles.

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Bionics Institute , East Melbourne , Victoria 3002 , Australia.
Department of Materials, Department of Bioengineering, and the Institute of Biomedical Engineering , Imperial College London , London SW7 2AZ , U.K.
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences , Monash University , Parkville , Victoria 3052 , Australia.


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.


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