Bio-friendly encapsulation of superoxide dismutase into vaterite CaCO3 crystals. Enzyme activity, release mechanism, and perspectives for ophthalmology

Binevski, P.V., Balabushevich, N.G., Uvarova, V.I., Vikulina, A.S. ORCID: 0000-0001-9427-2055 and Volodkin, D. ORCID: 0000-0001-7474-5329, 2019. Bio-friendly encapsulation of superoxide dismutase into vaterite CaCO3 crystals. Enzyme activity, release mechanism, and perspectives for ophthalmology. Colloids and Surfaces B: Biointerfaces, 181, pp. 437-449. ISSN 0927-7765

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Mesoporous vaterite CaCO3 crystals are nowadays one of the most popular vectors for loading of fragile biomolecules like proteins due to biocompatibility, high loading capacity, cost effective and simple loading procedures. However, recent studies reported the reduction of bioactivity for protein encapsulation into the crystals in water due to rather high alkaline pH of about 10.3 caused by the crystal hydrolysis. In this study we have investigated how to retain the bioactivity and control the release rate of the enzyme superoxide dismutase (SOD) loaded into the crystals via co-synthesis. SOD is widely used as an antioxidant in ophthalmology and its formulations with high protein content and activity as well as opportunities for a sustained release are highly desirable. Here we demonstrate that SOD co-synthesis can be done at pH 8.5 in a buffer without affecting crystal morphology. The synthesis in the buffer allows reaching the high loading efficiency of 93%, high SOD content (24 versus 15 w/w % for the synthesis in water), and order of magnitude higher activity compared to the synthesis in water. The enormous SOD concentration into crystals of 10−2 M is caused by the entrapment of SOD aggregates into the crystal pores. The SOD released from crystals at physiologically relevant ionic strength fully retains its bioactivity. As found by fitting the release profiles using zero-order and Baker-Lonsdale models, the SOD release mechanism is governed by both the SOD aggregate dissolution and by the diffusion of SOD molecules thorough the crystal pores. The latest process contributes more in case of the co-synthesis in the buffer because at higher pH (co-synthesis in water) the unfolded SOD molecules aggregate stronger. The release is bi-modal with a burst (ca 30%) followed by a sustained release and a complete release due to the recrystallization of vaterite crystals to non-porous calcite crystals. The mechanism of SOD loading into and release from the crystals as well as perspectives for the use of the crystals for SOD delivery in ophthalmology are discussed. We believe that together with a fundamental understanding of the vaterite-based protein encapsulation and protein release, this study will help to establish a power platform for a mild and effective encapsulation of fragile biomolecules like proteins at bio-friendly conditions.

Item Type: Journal article
Publication Title: Colloids and Surfaces B: Biointerfaces
Creators: Binevski, P.V., Balabushevich, N.G., Uvarova, V.I., Vikulina, A.S. and Volodkin, D.
Publisher: Elsevier
Date: 1 September 2019
Volume: 181
ISSN: 0927-7765
S0927776519303960Publisher Item Identifier
Rights: This article is available under the terms of the Creative Commons Attribution License (CC BY). You may copy and distribute the article, create extracts, abstracts and new works from the article, alter and revise the article, text or data mine the article and otherwise reuse the article commercially (including reuse and/or resale of the article) without permission from Elsevier. You must give appropriate credit to the original work, together with a link to the formal publication through the relevant DOI and a link to the Creative Commons user license above. You must indicate if any changes are made but not in any way that suggests the licensor endorses you or your use of the work.
Divisions: Schools > School of Science and Technology
Record created by: Linda Sullivan
Date Added: 06 Jun 2019 10:18
Last Modified: 30 Jul 2019 14:23

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