| 摘要 |
A method of forming microspheres containing a hydrophilic drug or agent for injection to provide localized treatment over a protracted time with sustained delivery in a therapeutically indicated rate band. The drug or agent is first dispersed or suspended as a micropulverized solid in an inert hydrophobic oil and sonicated with a non-aqueous solution of a biodegradable polymer. The dispersion is then stabilized in a second oil to remove solvent from the microspheres. Non-aqueous solvents are used throughout, and high drug concentrations are obtained simultaneously with enhanced control over a uniform and sustained delivery rate with extended duration of delivery. In vitro studies of ganciclovir in a silicone oil/fluorosilicone oil/PLGA system yield microsphere fractions that provide dose levels in a therapeutic range for CMV retinitis from only a single intravitreal injection that lasts substantially in excess of one month. The preparation method allows drug loading efficiencies above ninety percent. By protecting the drug in an inner phase carrier of biocompatible but not biodegradable oil, and forming biodegradable shells and pore-defining foliations within the microspheres, the rate of control of solvent erosion pathways into the microspheres is extended, and selection of the polymer and of the oils allow control over both the delivery rate and time. |
