A new hyaluronic acid pH sensitive derivative obtained by ATRP for potential oral administration of proteins

6533b7d3fe1ef96bd12600d0

RESEARCH PRODUCT

A new hyaluronic acid pH sensitive derivative obtained by ATRP for potential oral administration of proteins

Giovanna Pitarresi Giovanna Pitarresi Fabio Salvatore Palumbo Gaetano Giammona Calogero Fiorica Mauro Di Stefano Filippo Calascibetta

subject

Magnetic Resonance Spectroscopy Hyaluronic acid Size-exclusion chromatography Pharmaceutical Science Administration Oral ATRP Polymerization chemistry.chemical_compound Nephelometry and Turbidimetry Polymer chemistry Hyaluronic acid Copolymer Animals Chymotrypsin Denaturation (biochemistry)Solubility Rats Wistar Cells Cultured Atom-transfer radical-polymerization ATRP; Hyaluronic acid; pH sensitivity; α-Chymotrypsin Fibroblasts Hydrogen-Ion Concentration Ethylenediamines pH sensitivity Rats Quaternary Ammonium Compounds chemistry Proton NMR Chromatography Gel α-Chymotrypsin Derivative (chemistry)Nuclear chemistry

description

Atom transfer radical polymerization (ATRP) has been successfully employed to obtain a new derivative of hyaluronic acid (HA) able to change its solubility as a function of external pH and then to be potentially useful for intestinal release of bioactive molecules, included enzymes and proteins. In particular, a macroinitiator has been prepared by linking 2-bromo-2-methypropionic acid (BMP) to the amino groups of ethylenediamino derivative of tetrabutyl ammonium salt of HA (HA-TBA-EDA). This macroinititor, named HA-TBA-EDA-BMP has been used for the ATRP of sodium methacrylate (MANa) using a complex of Cu(I) and 2,2'-bipyridyl (Byp) as a catalyst. The resulting copolymer, named HA-EDA-BMP-MANa, has been characterized by (1)H NMR and size exclusion chromatography (SEC) analyses. A turbidimetric analysis has showed its pH sensitive behavior, being insoluble in simulated gastric fluid but soluble when pH increases more than 2.5. To confirm the ability of HA-EDA-BMP-MANa in protecting peptides or proteins from denaturation in acidic medium, α-chymotrypsin has been chosen as a model of protein molecule and its activity has been evaluated after entrapment into HA-EDA-BMP-MANa chains and treatment under simulated gastric conditions. Finally, cell compatibility has been evaluated by performing a MTS assay on murine dermal fibroblasts cultured with HA-EDA-BMP-MANa solutions.

year	journal	country	edition	language
2013-11-01

10.1016/j.ijpharm.2013.09.005 http://hdl.handle.net/10447/97212