Diffusion-controlled release of the theranostic protein-photosensitizer Azulitox from composite of Fmoc-Phenylalanine Fibrils encapsulated with BSA hydrogels.

ABSTRACT

Hydrogels offer a promising potential for the encapsulation and regulated release of drugs due to their biocompatibility and their tunable properties as materials. Only a limited number of systems and procedures enable the encapsulation of sensitive proteins. N-terminally fmoc-protected phenylalanine has been shown to self-assemble into a transparent, stable hydrogel It can be considered a supergelator due to the low amount of monomers necessary for hydrogelation (0.1% w/v), making it a good candidate for the encapsulation and stabilization of sensitive proteins. However, application options for this hydrogel are rather limited to those of many other fibril-based materials due to its intrinsic lack of mechanical strength and high susceptibility to changes in environmental conditions. Here, we demonstrate that the stability of a fibrillary system and the resulting release of the protein-photosensitizer Azulitox can be increased by combining the hydrogel with a tightly cross-linked BSA hydrogel. Azulitox is known to display cell-penetrating properties, anti-proliferative activity and has a distinctive fluorescence. Confocal microscopy and fluorescence measurements verified the maintenance of all essential functions of the encapsulated protein. In contrast, the combination of fibrillary and protein hydrogel resulted in a significant stabilization of the matrix and an adjustable release pattern for encapsulated protein.