Design of systems based on 4-armed star-shaped polyacids for indomethacin delivery

The 4-armed star-shaped copolymers containing methyl (meth)acrylate (MMA, MA) and (meth)acrylic acid (MAA, AA) units were synthesized by ATRP with the use of pentaerythritol (PTL) derivatives as tetrafunctional initiators and by post-polymerization modification to deprotect acidic units. The resultant MMA/MAA, MMA/AA, and MA/MAA based stars were varied by composition of arms using various initial proportions of comonomer pairs. The amphiphilic copolymers were self-assembled by dialysis or solvent evaporation methods into particles, which were also loaded with indomethacin (IMC). The sizes of polymeric aggregates were in the range of 100-200 nm, whereas drug loading efficiency was 10-85%. The in vitro release of IMC in phosphate buffer solution (PBS) demonstrated a higher rate of drug release at pH 5.0 than at 7.4. Drug release profiles can be adjusted by the content of the hydrophilic fraction (15-98%) and distribution of acidic units among arm chains (statistical vs. gradient vs. reverse gradient) as indicated by the broad range of the maximum drug release (10-85%).