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

作者：Fiorica Calogero; Pitarresi Giovanna^*; Palumbo Fabio Salvatore; Di Stefano Mauro; Calascibetta Filippo; Giammona Gaetano

来源：International Journal of Pharmaceutics, 2013, 457(1): 150-157.

DOI：10.1016/j.ijpharm.2013.09.005

• Hyaluronic acid
• ATRP
• pH sensitivity
• alpha-Chymotrypsin

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. %26lt;br%26gt;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%26apos;-bipyridyl (Byp) as a catalyst. %26lt;br%26gt;The resulting copolymer, named HA-EDA-BMP-MANa, has been characterized by H-1 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, alpha-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.

• 出版日期2013-11-30