DEVELOPMENT OF AN ORAL DELIVERY SYSTEM TO MODULATE THE RELEASE OF ANTHOCYANINS EXTRACTED FROM HASKAP BERRIES (LONICERA CAERULEA L.)

Abstract

Anthocyanins (ACNs) can be related to positive health benefits and are naturally present in many fruits. Haskap berries (Lonicera caerulea L.) have been traditionally associated with therapeutic properties, and as they are particularly rich source of ACNs, have the potential to develop into value-added products that are designed to maximize health benefits. In this thesis, a novel strategy to modulate the release of ACNs is proposed. This approach seeks to increase ACN retention in the stomach by designing a controlled delivery system to modulate the overall release and absorption of ACNs in the body, and reduce degradation due to intestinal pH or metabolism. Firstly, a theoretical physiologically-based, multi-compartmental pharmacokinetic (PBPK) model is developed to describe the fate of ACNs in vivo, where the role of the stomach and small intestine is recognized. Then, based on the evidence from recent literature, a strategy using gastroretentive systems as a platform for delivery of ACNs for therapeutic use (with type 2 diabetes as a model of degenerative disease) is proposed. Two novel gastroretentive systems (floating microspheres and an in situ gelling raft) were developed for oral delivery of ACNs. Firstly, parameters for ultrasound- assisted extraction of ACNs from haskap berries were studied using Response Surface Methodology (RSM). For the microspheres, ACN-rich extract was incorporated into non- floating calcium-alginate microparticles formed by extrusion/gelation method and optimized by RSM. Then the procedure was modified to incorporate calcium carbonate for gas generation to produce floating beads, where increasing the carbonate/alginate weight ratio from 0 to 3:4 resulted in different degrees of floatability, larger particles, higher encapsulation efficiency, and lower ACN release. The in situ gelling raft system with ACN-rich extract demonstrated suitable gelling and release characteristics. In both cases, the release of ACNs from the system was modulated where diffusion was the dominant mechanism. The raft system demonstrated a more sustained release of ACNs over time than the microspheres, and is recommended over the microspheres, due to simpler processing requirements and ease for scale-up. Thus, the in situ gelling system is recommended for further development.