Tunable drug release profiles from salicylate-based poly(anhydride-ester) matrices using small molecule admixtures

Abstract

Poly(anhydride-esters) with salicylic acid, a nonsteroidal anti-inflammatory drug, chemically incorporated into the polymer backbone provide high inherent drug loading. These poly(anhydride-esters) hydrolytically degrade to release salicylic acid over extended time periods (>30 days); however, an initial lag period of no salicylic acid release is observed. This lag period could be unfavorable in applications where immediate salicylic acid release is desired. Poly(anhydride-esters) with short (2 days) and long (11 days) lag periods were admixed with various small molecules as a means to shorten or eliminate the lag period. Salicylic acid, larger salicylic acid prodrugs, and 1:1 combinations of the two were physically admixed, each at 1%, 5%, and 10% (w/w). All admixtures resulted in immediate salicylic acid release and a decrease in glass transition temperatures compared to polymer alone. By varying the amounts of salicylic acid and salicylic acid prodrugs incorporated into the polymer matrix, immediate and constant salicylic acid release profiles over varied time periods were achieved.