Novel mucoadhesive system based on sulfhydryl-acrylate interactions.
We propose a novel cross-linked mucoadhesive system that can interact covalently with mucin type glycoprotein, thus providing both strong bonding to mucosa as well as ability to function as a sustained release matrix. The strong bonding results from Michael type addition reaction between an acrylate end group on a polymer and the sulfide end group of the mucin type glycoprotein. A proof of concept is provided using a polyehtylene glycol hydrogel formed in situ from polyehtylene glycol di-acrylate (PEG-DA) macromers. The ability of PEG-DA to create interactions with mucin type glycoproteins was verified using nuclear magnetic resonance (NMR) and rheology experiments. NMR studies have detected disappearance of the PEG-DA's vinyl protons upon mucin addition, whereas rheology measurements have shown a viscosity increase. These results provide an evidence for the formation of mucin-polymer covalent bond. The ability PEG-DA to attach to mucus and promote mucoadhesion was evaluated by tensile measurements. PEG-DA adhered at strength comparable to other covalently interacting mucoadhesive polymers. Furthermore, PEG-DA was found to be a suitable candidate for sustained release of the hydrophilic drug Ibuprofen.
Davidovich-Pinhas
Maya
M
Department of Chemical Engineering, Technion, 32000 Haifa, Israel.
Bianco-Peled
Havazelet
H
D000179:Acrylates / Q000737:chemistry*; D000818:Animals; D009077:Mucins / Q000737:chemistry; D009092:Mucous Membrane / Q000378:metabolism; D011092:Polyethylene Glycols; D011108:Polymers / Q000737:chemistry; D012212:Rheology; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013552:Swine; D014783:Viscosity
D000179:Acrylates; D009077:Mucins; D011108:Polymers; D013438:Sulfhydryl Compounds; C437167:poly(ethylene glycol)diacrylate; D011092:Polyethylene Glycols; C036658:acrylic acid