Zein as a versatile biopolymer: different shapes for different biomedical applications

In recent years, the interest regarding the use of proteins as renewable resources has deeply intensified. The strongest impact of these biomaterials is clear in the field of smart medicines and biomedical engineering. Zein, a vegetal protein extracted from corn, is a suitable biomaterial for all the above-mentioned purposes due to its biodegradability and biocompatibility.

The controlled drug delivery of small molecules, fabrication of bioactive membranes, and 3D assembly of scaffold for tissue regeneration are just some of the topics now being extensively investigated and reported in the literature. Herein, we review the recent literature on zein as a biopolymer and its applications in the biomedical world, focusing on the different shapes and sizes through which it can be manipulated.

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Introduction:

Amongst natural and synthetic materials, the former is more favorable considering the enormous availability of raw materials and their advantages in terms of manufacturing costs and low environmental impact. The search for biopolymers from natural and sustainable sources is one of the most important goals for the scientific community working on the boundary of chemistry and biology. The purpose is the fabrication of novel systems, which could be exploited for diverse applications in the biomedical field, such as targeted drug delivery, bioimaging, or tissue engineering. In the last decades, several natural and synthetic polymers have been investigated in order to develop biocompatible smart materials for the above-mentioned purposes.1,2 Proteins extracted from plants, in particular, have the benefit of being extensively available on earth and can be easily worked into different shapes, as fibers, films, micro-, and nanoparticles, or even hydrogels for medical applications.3,4 They are surely favored compared to carbohydrates because proteins carry many functional groups (such as amino and carboxyl groups) that can be exploited, for example, for labeling targeting molecules or in order to allow fast and stable crosslinking in 3D scaffolds’ fabrication. Moreover, the amphipathic nature of proteins gives them a versatile structure for easily and dynamically interacting with carbohydrates and lipids, just as at the interface between air and water.5
Many plant proteins, such as wheat gluten and soy proteins, have been used for fabricating biomaterials and have demonstrated biocompatibility in vitro but further issues arise due to their very poor solubility (either in water or organic solvents) and their inferior mechanical properties compared to the more well-known animal proteins, collagen and silk.6

Zein is a class of alcohol-soluble proteins rich in prolamin, approved as a Generally Recognized As Safe (GRAS) excipient in 1985 by the United States Food and Drug Administration (US-FDA) for the film coating of pharmaceuticals.7,8 In 2019, the global corn fiber market size was valued at USD 718.9 million and is expected to grow at a compound annual growth rate (CAGR) of 6.3% from 2020 to 2027.9 The rising usage of corn in the pharmaceutical field is expected to drive the market growth over the forecast period, supported by the simultaneously increasing consumption of food and beverage products.

According to solubility and sequence homology, we can classify zein in 4 groups: α-zein (19 and 22 kDa), which includes 70–85% of the total fraction of zein mass, β-zein (14 kDa), γ-zein (16 and 27 kDa), the second most abundant fraction, and δ-zein (10 kDa).10 All zein classes have several hydrophobic and neutral amino acids (as leucine, proline, and alanine) and also contain some polar amino acid residues, such as glutamine. Zein stands out from other proteins because it almost completely lacks lysine and tryptophan, including a few arginine and histidine residues. This amino acid composition is the reason for its unique solubility, mainly restricted to acetone, acetic acid, aqueous alcohols, and aqueous alkaline solutions.11

Novel biomedical applications of zein such as the controlled and targeted delivery of bioactive molecules and tissue engineering are the current research interests of the scientific community.

Zein-based formulations are focused on the properties possessed by this interesting natural material: highly resistant to heat, water, abrasion, and humidity; zein protein from corn is able to enhance the possibility for a longer shelf-life of biomolecules. A variety of biomedical fields take advantage of zein and research is nowadays extremely prolific; therefore, conscious of all the respectable works already published on zein, we acted rationally, in order to make our review relevant and innovative. We decided to reserve our attention to the very recent literature and strictly to those examples where zein has been used as the major component of innovative materials or applications, limiting those studies where zein protein has been used only as a minor additive. In this way, we reported a selected and high-impact summary of the whole literature concerning this material, focusing on the very recent applications of zein as an attractive promising biopolymer exclusively in the biomedical field and biomedical applications. Moreover, we rationalized the literature based on zein forms in terms of shape and size. We emphasized on chapter arrangement in order to help the reader find the desired application in a wide panning shot, from the 1D to the final 3D perspective. Furthermore, we think that this review can provide a multidisciplinary scenario of the emerging area of nanomedicine, which is increasingly becoming the glue between different scientific fields.

As touched upon, due to the huge number of cases that must be reported, we have divided the current survey into 3 chapters, following a logical thread based on the dimension of the zein-based system: in the first chapter zein nanoparticles and nanocomplexes are discussed; the second chapter is dedicated to fibers, films, and membranes; eventually, 3D objects as microbeads, gel, and scaffolds are examined in the third chapter.

Article information: Silvia Tortorella, Mirko Maturi, Veronica Vetri Buratti, Giulia Vozzolo, Erica Locatelli, Letizia Sambri and Mauro Comes Franchini. DOI: 10.1039/D1RA07424E (Review Article) RSC Adv., 2021, 11, 39004-39026