Photocrosslinking of dextran and polyaspartamide derivatives: a combination suitable for colon-specific drug delivery.
The aim of this study was to prepare and characterize novel hydrogels with polysaccharide-polyaminoacid structure, able to undergo an enzymatic hydrolysis in the colon and potentially useful for treating inflammatory bowel diseases (IBD). Starting materials were methacrylated dextran (DEX-MA) and methacrylated alpha,beta-poly(N-2-hydroxyethyl)-dl-aspartamide (PHM). These polymers were photocrosslinked by exposure of their aqueous solutions at 313 nm without photoinitiators. Different samples, shaped as microparticles, were obtained as a function of polymer concentration and irradiation time. FT-IR analysis confirmed the occurrence of a co-crosslinking between DEX-MA and PHM in all experimental conditions. Size analysis evidenced a narrow particle distribution and swelling studies, performed in twice-distilled water and simulated gastrointestinal fluids, showed a good affinity of these hydrogels towards the aqueous medium. DEX-MA/PHM based hydrogels undergo a negligible chemical hydrolysis, whereas they are partially degraded by dextranase. In vitro biological assays showed cell compatibility of these samples. Beclomethasone dipropionate (BDP), a drug recently proposed for the treatment of IBD was entrapped into a DEX-MA/PHM based hydrogel and its release was evaluated in the absence or in the presence of dextranase. Obtained release profiles suggest the potential use of BDP loaded DEX-MA/PHM based hydrogels for the treatment of IBD.
Pitarresi
Giovanna
G
Dipartimento di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Palermo, Italy. giopitar@unipa.it <giopitar@unipa.it>
Casadei
Maria Antonietta
MA
Mandracchia
Delia
D
Paolicelli
Patrizia
P
Palumbo
Fabio Salvatore
FS
Giammona
Gaetano
G
D001507:Beclomethasone / Q000008:administration & dosage / Q000737:chemistry; D018938:Caco-2 Cells; D002448:Cell Adhesion; D002470:Cell Survival / Q000187:drug effects; D003106:Colon / Q000187:drug effects*; D003432:Cross-Linking Reagents / Q000009:adverse effects / Q000737:chemistry* / Q000528:radiation effects; D003911:Dextrans / Q000009:adverse effects / Q000737:chemistry* / Q000528:radiation effects; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry* / Q000528:radiation effects; D004339:Drug Compounding; D004355:Drug Stability; D006801:Humans; D020100:Hydrogels / Q000009:adverse effects / Q000737:chemistry* / Q000528:radiation effects; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D008689:Methacrylates / Q000009:adverse effects / Q000737:chemistry* / Q000528:radiation effects; D009077:Mucins / Q000737:chemistry; D010316:Particle Size; D010455:Peptides / Q000009:adverse effects / Q000737:chemistry* / Q000528:radiation effects; D010777:Photochemistry
D003432:Cross-Linking Reagents; D003911:Dextrans; D004337:Drug Carriers; D020100:Hydrogels; D008689:Methacrylates; D009077:Mucins; D010455:Peptides; C008965:alpha,beta-poly((2-hydroxyethyl)-aspartamide); C514458:methacrylated dextran; D001507:Beclomethasone