Chemotherapeutic Delivery from a Self-Assembling Peptide Nanofiber Hydrogel for the Management of Glioblastoma.

PURPOSE: Localized chemotherapy has gained significant impetus for the management of malignant brain tumors. In the present study, we appraised the versatility of an in-situ gel forming self-assembling peptide, ac-(RADA)4 -CONH2 , as a biocompatible delivery depot of the chemotherapeutic drug doxorubicin (DOX) and the anticancer agent curcumin (CUR), respectively.

METHODS: The morphology and mechanical properties of ac-(RADA)4 -CONH2 were assessed with scanning electron microscopy (SEM) and rheological studies. The in vitro drug release from ac-(RADA)4 -CONH2 was monitored in phosphate-buffered saline pH 7.4. Distribution of the fluorescent actives within the peptide matrix was visualized with confocal laser scanning microscopy (CLSM). The in vitro biological performance of the ac-(RADA)4 -CONH2 -DOX and ac-(RADA)4 -CONH2 -CUR was evaluated on the human glioblastoma U-87 MG cell line.

RESULTS: SEM studies revealed that the ac-(RADA)4 -CONH2 hydrogel contains an entangled nanofiber network. Rheology studies showed that the more hydrophobic CUR resulted in a stiffer hydrogel compared with ac-(RADA)4 -CONH2 and ac-(RADA)4 -CONH2 -DOX, due to the interaction of CUR with the hydrophobic domains of the peptide nanofibers as confirmed by CLSM. In vitro release studies showed a complete DOX release from ac-(RADA)4 -CONH2 within 4 days and a prolonged release for ac-(RADA)4 -CONH2 -CUR over 20 days. An increased cellular uptake and a higher cytotoxic effect were observed for ac-(RADA)4 -CONH2 -DOX, compared with DOX solution. Higher levels of early apoptosis were observed for the cells treated with the ac-(RADA)4 -CONH2 -CUR, compared to CUR solution.

CONCLUSIONS: The current findings highlight the potential utility of the in-situ depot forming ac-(RADA)4 -CONH2 hydrogel for the local delivery of both water soluble and insoluble chemotherapeutic drugs.