title: Hyaluronic Acid-Based Nanogels Produced by Microfluidics-Facilitated Self-Assembly Improves the Safety Profile of the Cationic Host Defense Peptide Novicidin.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Formulation in nanogels could be a viable approach to improve the safety profile of host defence peptides.
authors: Section for Biologics, Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
authors: Jorrit J
authors: JJ
authors: Water
authors: YongTae
authors: Y
authors: Kim
authors: Morten J
authors: MJ
authors: Maltesen
authors: Henrik
authors: H
authors: Franzyk
authors: Camilla
authors: C
authors: Foged
authors: Hanne M
authors: HM
authors: Nielsen
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D001419:Bacteria / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003102:Colloids; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004563:Electrochemistry; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D044085:Microfluidics; D000080385:Nanogels; D010316:Particle Size; D011092:Polyethylene Glycols; D011094:Polyethyleneimine
chemical_list: D023181:Antimicrobial Cationic Peptides; D003102:Colloids; D000080385:Nanogels; C554278:novicidin; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D006820:Hyaluronic Acid