Cross-linked hyaluronic acid sub-micron particles: in vitro and in vivo biodistribution study in cancer xenograft model

Abstract

This paper focused on the biodistribution of the cross-linked hyaluronic acid (HA-NPs) sub-micron particles in tumor-bearing mice. Solvent-non solvent method followed glutaraldehyde cross-linking utilized for the fabrication of HA-NPs. Size measurement and morphological analysis were performed by dynamic light scattering and electron microscopy, respectively and the size found to be in the range of 200-400 nm. In vitro viability in LNCaP cell line was assessed by water soluble tetrazolium assay after 24 h of exposure to sub-micron particles and no toxicity was found to higher concentration of 3 mg/mL. Internalization of particles in prostate cancer cell LNCaP were studied by confocal microscopy with FITC labeled submicron particles and involvement of hyaluronan receptor mediated uptake/endocytosis was confirmed by competitive assay. Biodistribution studies were performed in xenograft prostate cancer mice model with fluorophore labeled particles and monitored in tumoral parenchyma with strong fluorescence, meanwhile very less signal in liver, kidney and spleen while no fluorescence found in lung after 24 h of systemic administration; that shown ability of this HA based system to recognize cancer tissue. These result fetched that hyaluronic acid based system is selective for tumoral site and can be utilized to deliver bioactives in specific (targeting) and controlled (temporal) manner to cancerous tissue.

Hyaluronic Acid Nanohydrogel Loaded With Quercetin Alone or in Combination to a Macrolide Derivative of Rapamycin RAD001 (Everolimus) as a New Treatment for Hormone‐Responsive Human Breast Cancer

“…Synthesis and characterization of hyaluronic acid hydrogel loaded with quercetin HA nanohydrogel was prepared by solvent-non solvent method, as previously described (Rosso et al, 2013). Briefly, a 0.5% w/v HA sodium salt solution in bidistilled water was added dropwise (1 ml/min) to an equal volume of DMSO (1:1v/v ratio) under magnetic stirring (75g).…”

New Treatment of Medullary and Papillary Human Thyroid Cancer: Biological Effects of Hyaluronic Acid Hydrogel Loaded With Quercetin Alone or in Combination to an Inhibitor of Aurora Kinase

“…HA hydrogel was prepared by solvent–non solvent method, as previously described (Rosso et al, ). Briefly, a 0.5% w/v HA sodium salt solution in bidistilled water was added dropwise (1 ml/min) to an equal volume of DMSO (1:1 v/v ratio) under magnetic stirring (75 xg).…”

“…A critical pathophysiological role in cancer cells is based on the production of low molecular weight HA by the action of hyaluronidase, in fact, most literature sources demonstrate that in several cancers, these enzymes are hypersecreted to enhance their progression and metastasis. Importantly, HA is a ligand of CD44 which is abundantly overexpressed in several cancer cells and associated with tumor progression; preclinical studies shows a correlation among cellular capacity for CD44‐mediated endocytosis, hyaluronan degradation, and tumor metastatic aggressiveness: the malignant cells that better internalize and degrade hyaluronan appear to be the most metastatic (Rosso et al, ).…”

Application of hyaluronic acid as carriers in drug delivery

“…Hyaluronic acid-spermine conjugate was also synthesized from the structure of high-mobility group protein to improve the transfection efficiency of encapsulated DNA (Xu & Kc, 2016 ). Hyaluronic acid receptors are abundant in some specific tissues such as liver, kidney, and most tumor tissues (Rosso et al., 2013 ). Hyaluronic acid can bind to the receptor on the cell surface and be absorbed into the cell through the endocytosis mediated by the hyaluronic acid receptor.…”