A new hyaluronic acid pH sensitive derivative obtained by ATRP for potential oral administration of proteins.
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.
Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, Plesso di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
Calogero
C
Fiorica
Giovanna
G
Pitarresi
Fabio Salvatore
FS
Palumbo
Mauro
M
Di Stefano
Filippo
F
Calascibetta
Gaetano
G
Giammona
D000284:Administration, Oral; D000818:Animals; D002478:Cells, Cultured; D002850:Chromatography, Gel; D002918:Chymotrypsin / Q000008:administration & dosage* / Q000737:chemistry; D005029:Ethylenediamines / Q000737:chemistry; D005347:Fibroblasts / Q000187:drug effects; D006820:Hyaluronic Acid / Q000031:analogs & derivatives* / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D009391:Nephelometry and Turbidimetry; D058105:Polymerization; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
D005029:Ethylenediamines; D000644:Quaternary Ammonium Compounds; C031234:ethylenediamine; D006820:Hyaluronic Acid; C009405:tetrabutylammonium; D002918:Chymotrypsin; C117608:alpha-chymotrypsin
ATRP; Hyaluronic acid; pH sensitivity; α-Chymotrypsin