The invention provides compositions and methods to treat microbial infections in animals, to inhibit the replication of microbes in infected cells, and to kill pathogens in infected cells. The methods can include administering to an animal in need of such treatment an effective antimicrobial amount of a composition comprising polyanhydride microparticles or nanoparticles that encapsulate a plurality of antimicrobial agents. The polyanhydride microparticles or nanoparticles can be, for example, copolymers of sebacic anhydride (SA) and 1,6-bis-(p-carboxyphenoxy)hexane (CPH) anhydride, copolymers of 1,8-bis(carboxyphenoxy)-3,6-dioxaoctane (CPTEG) anhydrides and 1,6-bis-(p-carboxyphenoxy)hexane (CPH) anhydride, or various combinations thereof. The microparticles or nanoparticles can accumulate in infected monocytes, dendritic cells, both, or on or in other infected cells, and degrade by surface erosion over a period of time to release the antimicrobial agents, thereby killing or inhibiting the microbes and treating the infection.
