Ovomucin nanoparticles: promising carriers for mucosal delivery of drugs and bioactive compounds

Akbari, A., Wu, J. Ovomucin nanoparticles: promising carriers for mucosal delivery of drugs and bioactive compounds. Drug Deliv. and Transl. Res. 7, 598–607 (2017). https://doi.org/10.1007/s13346-017-0406-3


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Drug delivery systems (DDS) are reported to reduce the side effects associated with conventional drug delivery caused on non-target cells. Besides synthetic materials, natural polymers such as lipids, proteins, and polysaccharides have attracted great interest for use in DDS due to their biocompatibility, biodegradability, and low toxicity. Mucoadhesive polymers could increase the ability of the polymeric particles’ adherence to the mucus layers and, thus, overcome the issue of the short transit time. Ovomucin, a glycoprotein accounting for 2.0–4.0% of total egg albumin, is a member of the mucin family, showing similarities to mucin from body mucus. It is composed of a carbohydrate-poor component (α-ovomucin, which constitutes α1 and α2 subunits) and a carbohydrate-rich component (β-ovomucin). A two-step method was developed to extract ovomucin with a purity greater than 90%. The objective of the study was to test the potential of ovomucin as a carrier in mucosal drug delivery. In this study, the mucoadhesive property, drug encapsulation efficiency, drug release, release kinetics, particle size, zeta potential, and morphology of ovomucin particles were studied.


Ovomucin with the purity of 92% was extracted from chicken fresh egg. The mucoadhesive property of ovomucin and three well known mucoadhesive polymers chitosan, polyacrylic acid (PAA), and alginate was measured by the following two methods: Tensile strength method and Rheology method. To evaluate the drug encapsulation efficiency of the three model drugs, suspensions of the drug-loaded particles with final concentrations of 0.5% ovomucin and 0.02% RF, 0.1%BB, or 0.125% CH at pH 5, 6.5, and 9 were prepared. The prepared CH-loaded ovomucin particles were used for release analysis. The release of CH was determined by incubating 40 mg CH-loaded particles in 40 ml of one of three release media with continuous shaking (75 rpm) at 37 °C in a water bath.

Analysis of Results

Three well-known mucoadhesive polymers, positively charged chitosan, negatively charged polyacrylic acid (PAA), and alginate, were chosen to compare the mucoadhesive property of negatively charged ovomucin. Maximum detachment force (MDF) and total work of adhesion (TWA) are indicators of the adhesiveness and viscoelastic properties of the mucoadhesive polymers. MDF of ovomucin was stronger than that of PAA, close to alginate, but weaker than chitosan; a similar trend was observed in TWA. Ovomucin is a long, extended molecule that forms a viscous solution or a weak gel due to physical entanglement. Unlike other food proteins that form a gel in the presence of heat or acidic conditions, 1% ovomucin dispersions can form fibrous weak gels in distilled water at room temperature. This property makes ovomucin an appropriate carrier for heat sensitive pharmaceutical or nutraceutical compounds. Encapsulation efficiency (EE) at the final concentrations of 0.5% ovomucin were ~25.4% for 0.02% RF at pH 6.5, ~87.7% for 0.02% BB at pH 5, and ~89.1% for 0.125% CH at pH 6.5. Since BB is a small molecule with pKa values of 5.63 and 6.53, electrostatic interactions were expected to form between BB and the positively charged amine groups of ovomucin at slightly acidic pHs; due to the presence of more positive groups in ovomucin at acidic pHs, EE for BB at pH 5 was higher than those at neutral and basic pHs (pH 6.5 and 9). The results showed that ovomucin particles were not resistant to gastric condition and easily released the encapsulated drug after 1 h.


The gelling ability of ovomucin at room temperature makes this protein suitable for encapsulating heat sensitive drugs. The ability of ovomucin nanoparticles for delivery of ionic molecules is better than that of non-ionic molecules. The EE of 88 and 89%, respectively, for negatively and positively charged molecules showed its potential for carrying many drugs and nutraceutical compounds. The fibrous structure of ovomucin gel and the presence of carboxyl, amine, and sialic groups provide a suitable medium to entrap different molecules using various interactions. Since the drug release profiles of ovomucin particles exhibited sustained releases and followed diffusion-based release models, the particles are resistant to degradation in both the simulated mucus media and intestinal fluid. Our assumption is that the moderate mucoadhesive property of ovomucin could help the nanoparticles to initially be immobilized in surface layers of mucus and then penetrate through mucus. Due to the similar negatively charged ovomucin particles and mucus, repulsive force might be a driving force for the penetration of the particles. Further research is required for studying the penetration of ovomucin particles through mucus.


Ovomucin, with a similar structure to mucin and gelation ability at room temperature, is a potential mucosal carrier. To evaluate this potential, the mucoadhesive property of ovomucin was studied by the tensile strength and rheology methods, and compared with three known mucoadhesive polymers, chitosan, polyacrylic acid (PAA), and alginate. Ovomucin particles were basically spherical in shape with an average size of ~572, 235 and 54 nm prepared at pH 5, 6.5, and 9, respectively. The absolute value of the zeta potential increased from ~ −51 mV at pH 5 to ~ −59 and −91 mV at pH 6.5 and 9, respectively. Drug loading efficiency of ovomucin particles for brilliant blue (negatively charged), riboflavin (non-ionic), and ciprofloxacin (positively charged) were ~87.7, 25.4, and 89.1%, respectively. The release of encapsulated ciprofloxacin was evaluated in phosphatebuffered saline (PBS), simulated intestinal fluid (SIF), and simulated gastric fluid (SGF). The mechanism of the releases was studied using different mathematical models: zero-order, first-order, Higuchi, Hixson-Crowell, and Korsmeyer-Peppas models. Approximately 61 and 67% of loaded ciprofloxacin were released from the particles over 7 h of incubation in PBS and SIF, respectively. The kinetics of drug releases in PBS and SIF followed the Fickian diffusion mechanism (KorsmeyerPeppas model). Therefore, ovomucin could function as a mucoadhesive carrier to efficiently encapsulate drugs and sustainably release them in the non-digestive and intestinal mucosal tissues.