A Review of the Biomaterial Applications of Zein

Peng Liu, Ying Li and Wei Zhou

Shanghai Institute of Quality Inspection and Technical Research, Shanghai 200040, China

Keywords: Zein, Biomaterial Applications.

Abstract:

Plant protein has increasingly inspired the interest of researchers due to its safety, wide sources, and high

performance and low cost. Zein, an important member of plant protein was used by the US FDA as a safe

excipient for drug film packaging in 1985. In the past 20 years, reports on the application of zein in the fields

of drug sustained-release material and tissue engineer scaffold materials have been constantly emerging,

making the application of zein in the field of biomedicine a research focus. This review summarizes some of

the application forms of zein in biomedicine, including drug loading, sustained-release material, and tissue

scaffolding in the form of microspheres, fibers, and films. It is expected that this review will provide ideas for

the use of zein in biomaterials industry.

1 INTRODUCTION

Zein is a degradable, hydrophobic plant protein

originally isolated from whole white corn and named

by John Gorham in 1821. According to protein

solubility and sequence homology, it can be further

subdivided into α-zein (19 and 22 kDa), β-zein (14

kDa), γ-zein (16 and 27 kDa), δ - Zein (10 kDa), of

which α-zein has the highest content in corn, reaching

70-85% (

Curtis, 1991)

. The zein originates is more

hydrophobic attributed to its large number of

hydrophobic amino acid residues, such as leucine,

proline, alanine. The unique amino acid composition

makes zein only soluble in acetone, acetic acid,

aqueous ethanol and alkaline aqueous solution.

Early period, Zein was used to make regenerated

fibers, but it was quickly replaced by synthetic fibers.

Until 1985, the US FDA approved zein excipient for

drug film coating as a GRAS mainly used in tablets

(Anonymous, 1985). Thus, zein began to enter the

period of medicinal use. In recent years, with some

reports of the application of zein in drug delivery and

tissue engineering, the application of zein has

gradually become a hot spot in the field of materials.

Zein can be made in various forms for using, and

there are four commonly application: microspheres,

nanoparticles, nanofibers and zein films.

Corresponding author

2 APPLICATION OF ZEIN

MICROSPHERES

Microspheres with an average diameter of 1 mm are

designed for intravenous injection and oral

administration of drugs. In 2005, Xinming Liu (Liu,

2005) prepared zein microspheres encapsulating

ivermectin (IVM) drugs by using phase separation

technology. The microspheres were characterized by

scanning electron microscope and laser scattering

particle size analyzer. In vitro studies showed that

zein microspheres are suitable for the sustained

release of IVM, and the system is suitable for use on

some biologically active substances that require

sustained release, See Figure 1.

3 APPLICATION OF ZEIN

NANOPARTICLES

Particles with at least one dimension less than 1000

nm are defined as nanoparticles (Cristina, 2007),

which have great potential for improving

bioavailability and bioactivity due to their unique

physicochemical properties (Emilie, 2010). The

insoluble nature of zein in water makes it a good

choice for the development of slow-release

biopolymer nanoparticles.

Liu, P., Li, Y. and Zhou, W.

A Review of the Biomaterial Applications of Zein.

DOI: 10.5220/0012013400003633

In Proceedings of the 4th International Conference on Biotechnology and Biomedicine (ICBB 2022), pages 77-81

ISBN: 978-989-758-637-8

 2023 by SCITEPRESS – Science and Technology Publications, Lda. Under CC license (CC BY-NC-ND 4.0)

Figure 1: Scanning electron micrographs of IVM-loaded zein microspheres (a) Before lyophilization (b) after lyophilization

(c) In vitro release profiles of IVM as a function of time from tabletted microspheres (d) from pepsin degraded tabletted

microspheres (Liu, 2005).

Cranberry proanthocyanidins (CPs) have

potential antioxidant functions and have certain

applications in reducing cardiovascular disease and

cancer. However, the oral bioavailability of CPs is

very low, which limits its further application. In 2011,

Tao Zou et al. (Zou, 2012) used an improved liquid-

liquid dispersion method to prepare cranberry

procyanidin-zein (CPs- Zein) nanoparticles, cell

culture experiments show that CPs encapsulated in

nanoparticles can reduce the toxicity to cells, See

Figure 2.

Figure 2: (A)Percentage of the cell viability, (B)the early stage of apoptosis (Zou, 2012).

Compounds with antioxidant effects have a

certain role in the prevention and treatment of some

cardiovascular diseases, tumors, etc., but most of

these antioxidant compounds have the characteristics

of low stability and low bioavailability, so the

development of new drug delivery methods for the

application of the compound is of great significance

(Huang, 2017). Gallic acid (GA) is an active

substance widely present in green tea, vegetables and

fruits, and has antioxidant, anti-inflammatory,

antibacterial and anti-tumor effects, but because

gallic acid is unstable under high temperature,

oxidation, light, etc., and the oral bioavailability is

low, so its application is limited (Wang, 2018). Jose

Agustin et al. (José, 2018) studied the preparation of

gallic acid-loaded zein nanoparticles by

electrospraying and demonstrated the potential

ability of such nanoparticles to protect gallic acid.

Figure 3. is the preparation process of gallic acid-

loaded zein nanoparticles.

ICBB 2022 - International Conference on Biotechnology and Biomedicine

Figure 3: Preparation process of gallic acid-loaded zein nanoparticles (José, 2018).

4 APPLICATION OF ZEIN

NANOFIBERS

The use of zein as fiber has a very long history. As

early as more than 100 years ago, Ostenberg reported

the first patent for the production of fiber with zein.

Since then, various dry or wet spinning methods to

prepare micro-sized corn gluten fibers have appeared

one after another. In 2013, Weidong Huang et al.

(Huang, 2013) used an improved coaxial

electrospinning process to prepare ibuprofen (IBU)-

loaded zein fibers, and in vitro dissolution

experiments showed that the drug-loaded fibers could

diffuse through typical Fickian diffusion. and the

mechanism maintains sustained release in 10 hours.

W. Nie et al. (Nie, 2012) prepared zein-

polyvinylpyrrolidone (PVP) microfiber materials by

electrospinning technology, He used ketoprofen as a

model drug. Vitro dissolution experiments showed

that the drug dissolution rate was related to the ratio

of PVP, and fibers with different dissolution rates can

be obtained by adjusting the ratio of zein and PVP.

The drug sustained release model is shown in Figure

Figure 4: Proposed drug release process of zein-coated tablets (Nie, 2012).

Afeesh Rajan Unnithan (Unnithan, 2014) mixed

cellulose acetate and zein, added streptomycin sulfate,

to obtain a nanofiber skeleton with antibacterial effect

utilizing electrospinning technology, applying

polyurethane as a substrate. The material has good

antibacterial properties, cytocompatibility, and

promotion of coagulation, this indicates the potential

application of this material in wound treatment.

A Review of the Biomaterial Applications of Zein

In addition to applications in drug delivery, zein

nanofibers have also begun to emerge as scaffolds for

tissue engineering. In 2015, Peng Liu (Liu, 2015)

used oxidized sucrose as a cross-linking agent to

prepare a zein nanofiber scaffold using 3D

electrospinning technology. The development laid the

foundation, See Figure 5.

Figure 5. SEM images of the views (a1 and a2) ,and CLSM images of the top 45°view (b1 and b2) of the electrospun 3D

ultrafine fibrous zein scaffolds, Weight loss of electrospun 3D ultrafine fibrous zein scaffolds crosslinked with glutaraldehyde

(GTA) and oxidized sucrose (OS) (c), Growth of preosteoblast cells on electrospun 3D ultrafine fibrous zein scaffolds

crosslinked with OS and GTA(d), Spreading of MC3T3 cells on electrospun 3D ultrafine fibrous zein scaffolds crosslinked

with OS and GTA(e1 and e2) (Liu, 2015).

5 APPLICATION OF ZEIN FILMS

The preparation of zein film is relatively easy, and it

can be obtained by solution casting and extrusion

(Zhang, 2015). Zein is dissolved in water and organic

solvents, and dried at room temperature or under

specified conditions, and then through the

hydrophobic interaction within the protein molecule.,

hydrogen bonds, disulfide bonds, etc. work together

to obtain a zein film (Krochta, 1994).

To verify the compatibility between zein films

and cells, Jian Dong (Dong, 2004) prepared zein

films for culturing human hepatocytes (HL-7702)

and mouse fibroblasts (NIH3T3). The results show

that there is no significant difference between zein

film and Corning microplate cultured cells. This

preliminary test shows that zein is a material with

good biocompatibility, which can be used in the

development of tissue engineering. Yi-Long Han

(Han, 2014) obtained a zein film with a thickness of

50-100 μm by casting protein on a coverslip, and the

obtained film had good transparency in a dry

environment. In vitro experiments with NIH 3T3

cells showed that the film performed similarly to

culture plates, and this material has potential

applications in cell culture substrates and

microfluidic devices. Figure 6. exhibits the

preparation method of zein film.

Figure 6: Preparation process of cast zein film (Han, 2014).

Bacterial infection on implanted devices is an

important clinical problem and is associated with

bacterial adhesion, bacterial proliferation, and

biofilm formation. Traditional treatments include

both systemic and topical antibiotic administration.

However, the side effects caused by systemic

ICBB 2022 - International Conference on Biotechnology and Biomedicine

administration are greater, so topical administration

has become an attractive means. Jian-Xi Fu et al. (Fu,

2009) prepared ciprofloxacin-loaded zein

microspheres by a phase separation method, and then

prepared zein microspheres containing the above-

mentioned. The solution of microspheres was poured

on the surface of a disc, and after the solvent

evaporated, a zein microsphere film (CF-MS film)

loaded with ciprofloxacin was obtained, and the

antibiotic-loaded zein film maintained antibacterial

activity for more than 6 days in experiments. The

material has potential application value in the

antibacterial of implanted devices.

6 CONCLUSION

Zein is an environmentally friendly and

biocompatible material. The promotion of its

industrial application contributes to the realization of

carbon peaking and carbon neutralization, so it has

been paid more and more attention by researchers.

Making zein in the form of particles, fibers and films

has been brilliant in the research fields of drug

delivery, drug sustained release, tissue engineering

scaffolds, etc. However, it should be noted that the

current research is basically still in the preclinical

stage, but we believe that through the continuous

efforts of researchers, zein will step into practical

clinical applications in the near future and benefit

mankind.

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A Review of the Biomaterial Applications of Zein