Hyaluronic Acid-Based Nano gels Produced by Microfluidics-Facilitated Self-Assembly Improves the Safety Profile of the Cationic Host Defense Peptide Novicidin

作者：Water Jorrit J; Kim YongTae; Maltesen Morten J; Franzyk Henrik; Foged Camilla; Nielsen Hanne M^*

来源：Pharmaceutical Research, 2015, 32(8): 2727-2735.

DOI：10.1007/s11095-015-1658-6

• antimicrobial peptides
• hyaluronic acid
• hydrogel nanoparticles
• microfluidics
• nanogels

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.

• 出版日期2015-8