The influence of structural morphology and swelling behaviour on diffusive transport of bioactives from crosslinked hydrogel systems
Creators: name: Morrish, Courtney
Publisher: name: RMIT University
Year: 2024
Subjects: classificationCode: 300602
subject: Food chemistry and food sensory science

description: To improve the benefits of foods, bioactive molecules can be incorporated but these are typically highly susceptible to common external stimuli, rendering them inactive. To protect these materials, entrapment within polymer gels has been explored. These polymer delivery vehicles can also sustain the diffusive release of the bioactive and target specific biological sites. Providing predictions on the kinetic movement of these bioactives within the gels and into the surrounding biological media is critical to evaluate their performance as delivery vehicles and to design effective release systems. This work aims to examine the diffusive release of bioactive compounds from biopolymer systems and relate the structure and composition of those gels to swelling parameters and molecular kinetics. Overall, this will contribute to the wider research by providing estimations of drug diffusion based on a number of system variables from a wide range of carriers. 

The first experimental chapter examines the development of a physically crosslinked alginate matrix. The alginate is crosslinked with calcium chloride and caffeine molecules were trapped within the bound network. The stoichiometric equivalent ratio of the calcium to alginate was varied to establish how the extent of crosslinking influenced swelling and volume changes. High levels of alginate addition caused network aggregation and inhomogeneity, thus the network rapidly eroded and did not swell as much as less crosslinked systems. The erosion of the matrix paired with the weaker physical crosslinks caused extremely fast diffusion and limited the sustained release. The microstructural parameters of the alginate gel were calculated using the modified ionic Flory-Rehner theory as alginate is anionic. The extent of crosslinking had some impact on the microstructural properties of mesh size and on the diffusion rates of the caffeine. The overall diffusion was anomalous, indicating that both the relaxation of the polymer chains and Fickian movement of the caffeine controlled the release rate.

In the second experimental chapter, a chitosan network physically crosslinked with trisodium phosphate was used to entrap and subsequently release caffeine. Whist the alginate was anionic, chitosan is cationic. Trisodium phosphate was used as the crosslinker, and caffeine was able to be entrapped within the matrix. High levels of crosslinking created semi-crystalline regions unsuitable for delivery vehicles whilst low levels formed a sol. Thus, an optimum crosslinking proportion was determined for this system. As with the alginate, the physically bound chitosan gels underwent extensive erosion during extended swelling studies. A strong correlation was found between the extent of crosslinking and the microstructural properties as the densely bound gels were less able to swell and had a smaller mesh size. The diffusion was also influenced by the extent of chain binding. Diffusion occurred rapidly in densely bound matrices due to the highly homogenous aggregated regions whilst lower crosslinked systems saw more sustained release due to network tortuosity and heterogeneity.

In the third experimental chapter, a chemically crosslinked system was instead used with gelatin crosslinked with genipin entrapping the caffeine. This system showed no erosion over the extended swelling timescales and so the release of the entrapped bioactive was sustained for even longer periods. The effect of the genipin on the gel structure was highly pronounced as low levels of addition saw higher swelling changes and a larger mesh size. This was able to be directly interrelated to the diffusion coefficients of the caffeine where release was markedly slower at high levels of genipin addition given the matrix’s dense structure, network rigidity and tortuosity. It was determined that the mesh size for successful diffusion must be much greater than the molecular diameter of the entrapped molecules. 

The final experimental chapter developed this work further with the use of a larger bioactive molecule. Lactoferrin was incorporated into a gelatin gel crosslinked with genipin. As with the smaller molecule, diffusion could be modulated through changing the crosslinking degree. The swellability of the matrix was also influenced by the amount of genipin as increased addition saw the network bound densely, hindering the infusion of water. The lactoferrin could be successfully released from the gel, although high levels of crosslinking meant that not all the molecules could diffuse freely, and some remained within the delivery vehicle. A strong relationship between the network morphology and the diffusion was determined mathematically as well. 

The final chapter summarises and highlights the contribution this work has made in the fields of food, polymer, and pharmaceutical sciences by linking morphological characteristics with both swelling and diffusive release. A correlation between these three components was repeatedly shown experimentally and theoretical expressions to describe this also further utilised. A comparison between physical and chemical crosslinking on diffusive release has been given, as well as the use of both a small and large bioactive molecule entrapped within the network. These results can be used to further develop delivery vehicles for the entrapment, protection and controlled release of bioactives from functional food systems.