Abstract: Sustained delivery compositions which modulate the release of incorporated prophylactic, therapeutic, and/or diagnostic agents, and methods of preparation and use thereof, are disclosed. The compositions include a biocompatible polymeric matrix; a prophylactic, therapeutic, and/or diagnostic agent dispersed within the polymeric matrix; and a monovalent cation component which is separately dispersed within the polymeric matrix. The monovalent cation component modulates the release of the incorporated agent from the polymeric matrix. The compositions can be prepared by dissolving a biocompatible polymer in a solvent to form a polymer solution, and separately dispersing a monovalent cation and a prophylactic, therapeutic, and/or diagnostic agent within the polymer solution. The polymer solution is then solidified to form a polymeric matrix, wherein a significant amount of the monovalent cations is dispersed in the polymeric matrix separately from the incorporated agent.