Use of whey proteins for encapsulation and controlled delivery applications

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Abstract

Whey proteins can be used as hydrogels and nanoparticle systems for encapsulation and controlled delivery of bioactive compounds. Whey protein concentrate (WPC) hydrogels exhibited pH-sensitive swelling behavior with minimum swelling ratio near the isoelectric point (pI) of whey proteins (∼5.1). The controlled drug release behavior of WPC hydrogels was studied using caffeine as a model drug. Consistent with the swelling behavior, the release of encapsulated model drug from the hydrogels was slower when the pH was below pI than it was at pH above pI. The swelling and release behavior of the WPC hydrogels can be changed easily with different layers of alginate coating. Nanoparticles of about 60 nm average particle size were prepared with beta-lactoglobulin (BLG) using a desolvation method by preheating the BLG solution to 60 °C. The stability of the particles was investigated by degradation experiments at neutral and acidic conditions with and without proteolytic enzyme.

Introduction

Whey proteins are valuable by-products from the cheese industry. They are used widely in a variety of foods primarily for their superior gelling and emulsification properties. β-Lactoglobulin (BLG) is the main whey protein component and its principal gelling agent. The physicochemical properties of the whey proteins suggest that they may be suitable for other novel food and non-food applications. For example, whey protein gels may be used as pH-sensitive hydrogels for the controlled delivery of biologically-active substances (Gunasekaran, Xiao, & Ould Eleya, 2006). A hydrogel can be defined as a three-dimensional network that exhibits the ability to swell in water and retains a significant fraction of water within its structure. There is a wide variety of hydrogels made from natural and synthetic polymers. Their ability to absorb water is due to the presence of hydrophilic groups such as –OH, –CONH–, –CONH2, –COOH, and –SO3H (Flory, 1953). Hydrogels can be neutral or ionic in nature. Because of their potential applications in controlled and site-specific drug release, the swelling behavior of hydrogels has been extensively studied. The driving force for swelling arises from the water–polymer thermodynamic mixing energy contribution to the overall free energy, which is coupled with an elastic polymer contribution (Kudela, 1985). For ionic hydrogels, the ionic interaction between charged polymer and free ions also contributes to swelling (Katchalsky, Lifson, & Eisenberg, 1951).

Various hydrogels have been developed as controlled drug release carriers using water-soluble, biodegradable polymeric materials (Gudeman and Peppas, 1995, Park, Choi, et al., 1998, Park, Song, et al., 1998, Wang et al., 2004, Wen and Stevenson, 1993) including synthetic or natural polymers. Among the natural polymers used to develop pH-sensitive hydrogels are alginates (Park, Choi, et al., 1998, Park, Song, et al., 1998) and chitosan (Deyao et al., 1993, Wang et al., 2004). The latter is usually cross-linked with other polymers such as poly(vinyl alcohol) (Wang et al., 2004) or poly(ether) (Deyao et al., 1993) using glutaraldehyde to produce semi-interpenetrating networks. Park, Choi, et al. (1998) reported that pH-sensitive hydrogels can be prepared from egg albumin simply through heat-induced gelation. They investigated the effect of gel preparation conditions, particularly the initial pH of the protein solution, on the swelling of dried albumin gel in phosphate buffer solutions. The albumin hydrogels exhibited pH-sensitive swelling behavior; the degree of swelling was low around the protein isoelectric point (pI) (pH 4) and increased with pH.

Strong or weak heat-induced gels, with high or low water-holding capacity may be prepared from whey protein solutions simply by adjusting several of the gelation variables: concentration, pH, ionic strength, etc. Thus, it is possible to design heat-induced whey protein gels with good pH-sensitivity, tailored permeability, and mechanical properties that can be used as bioactive carriers. The advantages of using whey protein-based gels as potential devices for controlled release of bioactives is that they are entirely biodegradable and there is no need for any chemical cross-linking agents in their preparation. These are two of the major requirements for wide use of hydrogels not only in the pharmaceutical area but also in many food and bioprocessing applications.

Furthermore, whey proteins may also be formed into nanoparticles. Nanoparticles are matrix systems of a dense polymeric network in which an active molecule may be dispersed throughout the matrix (Nakache, Poulain, Candau, Orecchioni, & Irache, 2000). Since nanoparticles are submicron and sub-cellular in size, they have versatile advantages for targeted, site-specific delivery purposes (Vinagradov, Bronich, & Kabanov, 2002) as they can penetrate circulating systems and target sites. The nanoparticles offer the feasibility to entrap drugs or bioactive compounds within but not chemically bound to them.

Various biocompatible and biodegradable biopolymers have been used in the formation of nanoparticles to maximize delivery efficiency and increase the desirable benefits (Coester et al., 2000, Kreuter, 1994, Rhaese et al., 2003). Albumin nanoparticles have been extensively investigated with respect to their preparation methods and release properties (Langer et al., 2003, Loo et al., 2004, Vural et al., 1990). Human serum albumin (HSA) and bovine serum albumin (BSA) have been used as natural matrix materials for delivery devices (Brannon-Peppas, 1995).

The objectives of this research were to investigate the use of whey proteins as (1) pH-sensitive hydrogels and (2) nanoparticle systems.

Section snippets

Gel preparation

Whey protein concentrate (WPC) powder obtained from a commercial source (Davisco Foods International Inc., Eden Prairie, MN, USA) was used. This powder contained 82.5% protein, 6.8% fat, 3.4% ash, and 6.5% lactose (data supplied by the manufacturer). Two sets of WPC gels were prepared: Set 1: WPC concentration = 15% (w/v) and pH = 5.1, 5.7, 6.2, 6.8, 7.2, and 10.0; Set 2: pH = 10.0 and WPC concentration = 12%, 15%, and 18%.

Gels were prepared in cylindrical (10-mm inner diameter, 40-mm long) stainless

Effect of swelling medium pH on the kinetic and equilibrium swelling

The swelling kinetics of 15% WPC hydrogel denatured at pH 10.0 kept in different swelling media pHs are shown in Fig. 1. The SR of WPC hydrogels is sensitive to the swelling medium pH; the higher the swelling medium pH, the faster the swelling. At pH 10.0, the gels reached the equilibrium SR value in about 50 min while at pH 1.8, it took almost twice as long.

The kinetics of swelling may be understood by considering several simultaneous effects. The contours of time vs. penetrant uptake curve

Conclusions

Whey proteins can be used as hydrogels and/or nanoparticles systems for controlled release of bioactive compounds. As hydrogels, they exhibit pH-sensitive swelling ability especially at pH above their isoelectric point. The release kinetic of the hydrogels parallel that of their swelling ability. The release properties can be conveniently altered by appropriately coating with sodium alginate. Nanoparticles of sub-100-nm size can be prepared from beta-lactoglobulin (BLG). The average particle

Acknowledgement

We thank Davisco Foods International Inc. for providing the whey proteins for our study.

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