ABSTRACT
Multilayer films that decompose in the presence of lactate were prepared by depositing phenylboronic acid-modified poly(allylamine) (PBA-PAH) and poly(vinyl alcohol) (PVA) on a lactate oxidase (LOx) layer. The layers adhered through boronate ester bonds. The resulting LOx(PBA-AH/PVA)10 film was stable in pH 7.4 solution but decomposed following the addition of lactate. The carbon-boron bonds in PBA residues were cleaved by oxidative reaction with H2O2 produced by the enzymatic reaction of LOx. Approximately 90% of the film decomposed following exposure for 120 and 30min to 0.05 and 20mM lactate at pH 7.4, respectively. The multilayer film therefore decomposed under conditions comparable to the extracellular environment of tumors (20mM lactate at pH 6.5). Our results show that LOx/(PBA-PAH/PVA)10 multilayer film could be used for cancer drug delivery systems.
Subject(s)
Boronic Acids/chemistry , Drug Carriers/chemistry , Lactic Acid/chemistry , Polyamines/chemistry , Polyvinyl Alcohol/chemistry , Humans , Hydrogen-Ion Concentration , Membranes, Artificial , Mixed Function Oxygenases/chemistry , Neoplasms/metabolism , Oxidation-Reduction , Surface PropertiesABSTRACT
Hydrogen peroxide (H2O2)-sensitive layer-by-layer films were prepared based on combining phenyl boronic acid (PBA)-modified poly(allylamine) (PAH) with shikimic acid (SA)-modified-PAH through boronate ester bonds. These PBA-PAH/SA-PAH multilayer films could be prepared in aqueous solutions at pH 7.4 and 9.0 in the presence of NaCl. It is believed that the electrostatic repulsion between the SA-PAH and PBA-PAH was diminished and the formation of ester bonds between the SA and PBA was promoted in the presence of NaCl. These films readily decomposed in the presence of H2O2 because the boronate ester bonds were cleaved by an oxidation reaction. In addition, SA-PAH/PBA-PAH multilayer films combined with glucose oxidase (GOx) were decomposed in the presence of glucose because GOx catalyzes the oxidation of D-glucose to generate H2O2. The surfaces of CaCO3 microparticles were coated with PAH/GOx/(SA-PAH/PBA-PAH)5 films that absorbed insulin. A 1 mg quantity of these particles released up to 10 µg insulin in the presence 10 mM glucose under physiological conditions.
