Design self-assembling peptide hydrogel for targeted cancer drug delivery Siyuan Dong 1 , Aline F. Miller 1,2 , Alberto Saiani 2 1 Manchester Institute of Biotechnology, The University of Manchester, UK 2 School of Engineering, The University of Manchester, UK Introduction Self-assembling peptide based hydrogels have attracted considerable attention in the past decade in the drug delivery field [1]. One family of self-assembling peptide which has shown great promise as far as hydrogel design is concerned are β-sheet forming peptides [2]. In order to design and formulate hydrogels loaded drugs composites it is essential to understand how the drug and the peptide network interact and how the drug diffusion can be controlled. For this purpose we designed two novel peptides, E(FKFE) 2 (-1) and K(FEFK) 2 (+1) that form hydrogels at pH7. As a model drug compound we chose a series of fluorescein labelled polymers (dextran and poly-l-lysine) with varying molecular weights and charges allowing us to probe the effect of guest molecule hydrodynamic size and electrostatic interaction on its diffusion. Interleukin 21 was loaded into two different charge of peptide hydrogels to investigate the release profile and applied on peripheral blood mononuclear cell (PBMC) to study the cell marker expression. Results and discussion The formation of β-sheet rich fibres was confirmed in both peptide hydrogels by FTIR. The size of fibres was measured by TEM and SAXS. The dextran was anionic and poly-l-lysine was cationic. As a result, very different release profiles were observed in the two peptide hydrogel systems. Dextran probes released faster from E(FKFE) 2 hydrogel but they were trapped in K(FEFK) 2 which could anticipate that the electrostatic interaction existed between peptide hydrogel and probe. Poly-L-Lysine with 28kDa presented a slow release process form K(FEFK) 2 hydrogel who carried the same charge molecules. However, it cannot release out from E(FKFE) 2 hydrogel. Further, K(FEFK) 2 hydrogel loaded with poly-L-Lysine was found to swell significantly. This is thought to be due to the strong electrostatic repulsion existing between the poly-L-Lysine and the peptide fibres resulting in the overall hydrogel fibres being pushed apart and leading to swelling. The good cell viability results indicated the peptide hydrogels present good biocompatibility and IL21 performed good control release kinetics in E(FKFE) 2 gel. Conclusion Our work clearly shows the potential of using rational design to create hydrogel suitable for the delivery of large drug molecules for specific needs. IL21 loaded into our peptide hydrogel prolong the half live of drug, enlarge the therapeutic window and might activate CD4+, CD8+ and CD56+ cell marker which is able to apply into immune cancer therapy. References 1. R. Huang, W. Qi, L. Feng, R. Su, and Z. He, ‘‘Self-assembling peptide-polysaccharide hybrid hydrogel as a potential carrier for drug delivery,’’ Soft Matter, 2011. 2. D. Roberts, C. Rochas, A. Saiani, and A. F. Miller, “Effect of peptide and guest charge on the structural, mechanical and release properties of β-sheet forming peptides,’’ Langmuir, 2012
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