1. Tailoring drug release kinetics from peptide hydrogels Mohamed A
Tailoring drug release kinetics from peptide hydrogels Mohamed A. Elsawy1,3, Luis A. Castillo Diaz2,3, Aline F. Miller2,3 and Alberto Saiani1,3,* 1School of Materials, University of Manchester, UK. 2School of Chemical Engineering and Analytical Sciences, University of Manchester, UK. 3Manchester Institute of Biotechnology, University of Manchester, UK. *Correspondence to Webpage:
Peptide self-assembly
β -sheets
Fibres formation
Hydrophilic
Hydrophobic
Drug-release
Concept and Vision... pH
Fibres
entanglement
In-vitro Drug Release Studies
Drug Encapsulation in Peptide Hydrogel
Drug-Gel
Injection
Ionic self-complementary
peptides self-assembly into β-sheets
β-sheets fibre formation
Clinical Studies
Selective Delivery
To Target Site of Action
In-vivo Drug
Release Studies
Controlled Release Has Been Made Possible...
Fibre Charge
β-sheet peptide hydrogel formulations with different fibre charge were designed to control the release kinetics of Doxorubicin (Dox), by varying the number of Lys residues in the peptide sequence.
Gel Hybrids
Further tailoring of Dox release rate was achieved by
formulating hybrid hydrogels of mixed peptides.
Peptides used
FEFKFEFK (F8) Neutral (0, 2 Lys)
FEFKFEFKK (F9) Cationic (+1, 3 Lys)
FKFEFKFK (SC) Cationic (+2, 3 Lys)
KFEFKFEFKK (BE) Cationic (+2, 4 Lys)
FEFEFKFE (FE) Anionic (-2, 1 Lys)
Peptide mix. conc. 14 mM
Figure 3 Dox release kinetics from FE/F8 hybrid gels with 14 mM peptide mixture concentration
Gel Concentration
Peptide
Dox release rate was controlled by varying the peptide concentration.
Gels conc. 14 mM
Doxorubicin.HCl
(Anti-Cancer Drug)
Figure 1 Dox release kinetics from gels with various fibre charge
Figure 5 Reduction of 3T3 cells proliferation rate treated with Dox (240nM)-F8 gel formulations with various peptide concentrations
Figure 4 Dox release kinetics from F8 gels with various peptide concentrations
Both the fibre charge and number of Lys residues
control the drug release kinetics
Gels conc. 14 mM
The higher the gel concentration the slower drug release kinetics
Figure 2 Reduction of 3T3 cells proliferation rate treated with Dox (240nM)-gel (14mM) formulations with various fibre charge
In Conclusion…
Dox release rate from β-sheet peptide hydrogels was controlled by varying the fibre charge, number of Lys residues and gel concentration. Gel hybrids provided a new tool for further tailoring of the drug release kinetics. In-vitro cell-based assays showed that the formulations with faster Dox release kinetics caused faster reduction in 3T3 cells proliferation rates and vice versa. In summary, we have shown how the drug-peptide interactions can be manipulated to control the release kinetics of Dox from these hydrogels.
Acknowledgments
The authors would like to thank the Engineering and Physical Sciences Research Council (EPSRC Grant no: EP/K016210/1) for the financial support of this research