In vitro characterization of physico-chemical properties, cytotoxicity, bioactivity of urea-crosslinked hyaluronic acid and sodium ascorbyl phosphate nasal powder formulation

Int J Pharm. 2019 Mar 10:558:341-350. doi: 10.1016/j.ijpharm.2019.01.012. Epub 2019 Jan 16.

Abstract

An innovative lyophilized dry powder formulation consisting of urea-crosslinked hyaluronic acid (HA-CL) and sodium ascorbyl phosphate (SAP) - LYO HA-CL - SAP- was prepared and characterized in vitro for physico-chemical and biological properties. The aim was to understand if LYO HA-CL - SAP could be used as adjuvant treatment for nasal inflammatory diseases. LYO HA-CL - SAP was suitable for nasal delivery and showed to be not toxic on human nasal septum carcinoma-derived cells (RPMI 2650 cells) at the investigated concentrations. It displayed porous, polygonal particles with unimodal, narrow size distribution, mean geometric diameter of 328.3 ± 27.5 µm, that is appropriate for nasal deposition with no respirable fraction and 88.7% of particles with aerodynamic diameter >14.1 µm. Additionally, the formulation showed wound healing ability on RPMI 2650 cells, and reduced interleukin-8 (IL-8) level in primary nasal epithelial cells pre-induced with lipopolysaccharide (LPS). Transport study across RPMI 2650 cells showed that HA-CL could act not only as carrier for SAP and active ingredient itself, but potentially also as mucoadhesive agent. In conclusion, these results suggest that HA-CL and SAP had anti-inflammatory activity and acted in combination to accelerate wound healing. Therefore, LYO HA-CL - SAP could be a potential adjuvant in nasal anti-inflammatory formulations.

Keywords: Anti-inflammatory; Hyaluronic acid; Nasal diseases; Sodium ascorbyl phosphate; Urea-crosslinked hyaluronic acid; Wound healing.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / chemistry
  • Administration, Intranasal
  • Adult
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / chemistry
  • Ascorbic Acid / administration & dosage
  • Ascorbic Acid / analogs & derivatives*
  • Ascorbic Acid / chemistry
  • Cell Line
  • Cell Survival / drug effects
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology
  • Humans
  • Hyaluronic Acid / administration & dosage*
  • Hyaluronic Acid / chemistry
  • Interleukin-8 / immunology
  • Lipopolysaccharides / pharmacology
  • Nasal Mucosa / immunology
  • Powders
  • Urea / administration & dosage*
  • Urea / chemistry
  • Wound Healing / drug effects
  • Young Adult

Substances

  • Adjuvants, Immunologic
  • Anti-Inflammatory Agents
  • CXCL8 protein, human
  • Interleukin-8
  • Lipopolysaccharides
  • Powders
  • ascorbate-2-phosphate
  • Urea
  • Hyaluronic Acid
  • Ascorbic Acid