Physical and structural characteristics of acrylated poly(ethylene glycol)-alginate conjugates

Transmucosal delivery of therapeutic agents is a non-invasive approach that utilizes human entry paths such as the nasal, buccal, rectal and vaginal routes. Mucoadhesive polymers have the ability to adhere to the mucus layer covering those surfaces and by that promote drug release, targeting and absorption. We have recently demonstrated that acrylated polymers display enhanced mucoadhesive properties due to their ability to covalently attach to mucus type glycoproteins. We have synthesized an acrylated poly(ethylene glycol)-alginate conjugate (alginate-PEGAc), a molecule which combines the gelation ability of alginate with the mucoadhesion properties arising from both the characteristics of poly(ethylene glycol) and the acrylate functionality. In the current investigation we introduce an in-depth characterization of the thermal, mechanical and structural properties of alginate-PEGAc aimed at gaining a better knowledge of its structure-function relations. The thermal stability, evaluated by thermal gravimetric analysis and differential scanning calorimetry, was compared with that of alginate and the intermediate product thiolated alginate. Dehydration at temperatures up to 200 °C was detected for all samples, followed by distinctive decomposition steps arising from the decomposition of the polymer backbone and side-chains. The nanostructure of the solutions and gels was evaluated from small angle X-ray scattering patterns, to which the "broken rod linked by flexible chain" model was fitted, and from rheology measurements. The maxima arising from electrostatic repulsion between the highly charged alginate chains was diminished for both modified alginate samples, suggesting that modification led to electrostatic screening. Alginate, thiolated alginate and alginate-PEGAc cross-linked with calcium ions demonstrated similar scattering patterns. However, different scattering intensities, gel strengths, and gelation kinetics were observed, suggesting a decrease in the cross-linking density in the order alginate>thiolated alginate>alginate-PEGAc. These results were attributed to the increased size of the grafted side groups, which interfere with the gelation process. Examining the effect of the method of alginate-PEGAc gelation (physical or chemical) has shown that additional UV irradiation of calcium cross-linked gels did not cause a significant change in the network structure and strength. It seems that the concentration of the acrylated end group is not high enough to create a chemically cross-linked network.