PURPOSE: Cationic host defence peptides constitute a promising class of therapeutic drug leads with a wide range of therapeutic applications, including anticancer therapy, immunomodulation, and antimicrobial activity. Although potent and efficacious, systemic toxicity and low chemical stability have hampered their commercial development. To overcome these challenges a novel nanogel-based drug delivery system was designed. METHOD: The peptide novicidin was self-assembled with an octenyl succinic anhydride-modified analogue of hyaluronic acid, and this formulation was optimized using a microfluidics-based quality-by-design approach. RESULTS: By applying design-of-experiment it was demonstrated that the encapsulation efficiency of novicidin (15% to 71%) and the zeta potential (-24 to -57 mV) of the nanogels could be tailored by changing the preparation process parameters, with a maximum peptide loading of 36 ± 4%. The nanogels exhibited good colloidal stability under different ionic strength conditions and allowed complete release of the peptide over 14 days. Furthermore, self-assembly of novicidin with hyaluronic acid into nanogels significantly improved the safety profile at least five-fold and six-fold when tested in HUVECs and NIH 3T3 cells, respectively, whilst showing no loss of antimicrobial activity against Escherichia coli and Staphylococcus aureus. CONCLUSION: Formulation in nanogels could be a viable approach to improve the safety profile of host defence peptides.
PURPOSE: Cationic host defence peptides constitute a promising class of therapeutic drug leads with a wide range of therapeutic applications, including anticancer therapy, immunomodulation, and antimicrobial activity. Although potent and efficacious, systemic toxicity and low chemical stability have hampered their commercial development. To overcome these challenges a novel nanogel-based drug delivery system was designed. METHOD: The peptide novicidin was self-assembled with an octenyl succinic anhydride-modified analogue of hyaluronic acid, and this formulation was optimized using a microfluidics-based quality-by-design approach. RESULTS: By applying design-of-experiment it was demonstrated that the encapsulation efficiency of novicidin (15% to 71%) and the zeta potential (-24 to -57 mV) of the nanogels could be tailored by changing the preparation process parameters, with a maximum peptide loading of 36 ± 4%. The nanogels exhibited good colloidal stability under different ionic strength conditions and allowed complete release of the peptide over 14 days. Furthermore, self-assembly of novicidin with hyaluronic acid into nanogels significantly improved the safety profile at least five-fold and six-fold when tested in HUVECs and NIH 3T3 cells, respectively, whilst showing no loss of antimicrobial activity against Escherichia coli and Staphylococcus aureus. CONCLUSION: Formulation in nanogels could be a viable approach to improve the safety profile of host defence peptides.
Authors: Matthew L Mayer; Christoph J Blohmke; Reza Falsafi; Chris D Fjell; Laurence Madera; Stuart E Turvey; Robert E W Hancock Journal: J Immunol Date: 2012-12-21 Impact factor: 5.422
Authors: Kelly C L Mulder; Loiane A Lima; Vivian J Miranda; Simoni C Dias; Octávio L Franco Journal: Front Microbiol Date: 2013-10-31 Impact factor: 5.640
Authors: Bowen Qi; Ayrianne J Crawford; Nicholas E Wojtynek; Megan B Holmes; Joshua J Souchek; Graca Almeida-Porada; Quan P Ly; Samuel M Cohen; Michael A Hollingsworth; Aaron M Mohs Journal: Nanomedicine Date: 2018-01-09 Impact factor: 5.307