Implant compositions for the unidirectional delivery of drugs to the brain

Abstract

The overall objective of this study was to design and characterize the properties of a bioadhesive trilayer sustained-release implant device for the unidirectional local delivery of anticancer compounds to the brain following the removal of glioblastoma multiforme tumors. Using acetaminophen as a model drug compound, we compressed trilayer wafers that contained (i) a bioadhesive layer, (ii) a drug layer that contained a lipid and a pore-forming hydrophilic polymer, and (iii) a third layer comprising a lipid substance. To maintain a unidirectional pathway of drug release from these trilayer wafers, the edges and the surface lipophilic layer were coated with molten wax followed by cooling of the wafer. These wafers were subsequently heat cured to promote interlayer adhesion in the device. Polyethylene oxide was utilized both as the bioadhesive layer and the pore-forming hydrophilic polymer. Glyceryl behenate was employed as the lipid. The drug release properties of the trilayer wafer were a function of (i) the molecular weight and concentration of polyethylene oxide in the drug-containing lipid layer, (ii) the presence of the bioadhesive layer on the wafer, and (iii) the lipid coating applied to the top and sides of the delivery system. The unidirectional release of the drug occurred from the device through the bioadhesive layer, and zero-order release kinetics resulted over a 10-day period after a 3-day lag time. During this period, <10% of the drug had been released from the wafer. All of the drug was released by 21 days.