Rational design of food-grade polyelectrolyte complex coacervate for encapsulation and enhanced oral delivery of oenothein B

Abstract

Oenothein B (OeB), a dimeric macrocyclic ellagitannin isolated from eucalyptus leaves has been demonstrated as a promising natural bioactive compound for its remarkable antitumor, antioxidant, anti-inflammatory and immunomodulating effects. Unfortunately, early study indicates that OeB has quite low bioaccessibility for oral consumption due to their susceptibility to decomposition both in vitro and in vivo. Herein, we report the design and synthesis of food-grade polyelectrolyte complex coacervate using caseinophosphopeptides (CPPs) and chitosan (CS) to encapsulate OeB for enhanced protection through gastrointestinal (GI) tract. Turbidimetric titration, dynamic light scattering (DLS), ζ-potential and scanning electric microscopy (SEM), as well as theoretical calculations based on principle of charge neutralization, were conducted to provide tentative and quantitative description for phase behavior in formation and disassociation of the complex. The optimum fabrication conditions were found to be at pH 5.5, with CPP : CS at 1 : 1, using CS of high molecular weight (980 kDa). The genipin cross-linking protected the system from disassembling in harsh acidic environments. The best cross-linking conditions were found to be 0.6 mg ml⁻¹ genipin addition at 4 h cross-linking reaction time. The particle size and zeta potential of the nanoparticles varied from 200 to 300 nm and +20 to +24.2 mV, respectively. Scanning electron microscopy (SEM) revealed a spherical coacervate phase. Results from in vitro release study proved that controlled release of OeB through GI tract using CPP–CS nanoparticles cross-linked with genipin was achievable.