Abstract:
Self-assembled peptide gels have generated interest as antibacterial materials to prevent biomaterial-related
infections but these peptides are often associated with poor proteolytic stability. Efforts have been made to
stabilize peptides by incorporating non-natural amino acids and/or linkages but complexation with polymers
have not been explored. Therefore, we developed self-assembled peptide/chitosan gels, Boc-D-Phe-γ4
-L-Phe-PEA
(NH007)/chitosan and Boc-L-Phe-γ4
-L-Phe-PEA (NH009)/chitosan, by complexing dipeptide NH007 or NH009
with chitosan in DMSO:acetic acid. The gels were characterized using SEM, FTIR, contact angle, and rheology
data and found to exhibit excellent viscoelastic and self-healing characteristics. Complexation with chitosan led
to an increase in stability against proteolytic degradation. Peptide/chitosan gels showed broad spectrum antibacterial activities against Gram-negative and Gram-positive bacteria, such as Escherichia coli, Pseudomonas
aeruginosa, Staphylococcus aureus, and Bacillus subtilis at a high inoculum of 107
–108 cfu/mL. NH007/chitosan
gels showed 70–75% inhibition, whereas NH009/chitosan showed 78–81% inhibition and NH009/chitosan gels,
in particular, showed strong antibacterial activity against pathogenic strain of P. aeruginosa. A unique feature of
these gels is that the antibacterial activities did not decrease gradually but were sustained for up to 48 h. The
mechanistic studies using SEM and HR-TEM indicated interaction of gels with bacterial membrane components,
leading to cell lysis. The MTT and LDH assays indicated > 90% cell viability and only 8–10% toxicity towards
NIH 3T3 fibroblast cells. Thus, peptide/chitosan gels developed in the present work showed improved proteolytic stability and sustained antibacterial activities and, therefore, may be used for preventing biomaterialrelated infections.
