RESUMO
PURPOSE: The pH-responsive copolymer micelles are widely used as carriers in drug delivery system, but there are few micro-level mechanistically explorations on the pH-triggered drug release. Here we elucidate the relationship between drug release behavior of four/six-arms star copolymer micelles and the copolymer structures. METHOD: The net cumulative drug release percentage (En) was taken as the dependent variables, block unit autocorrelation descriptors as independent variables. The quantitative structure-property relationship models of drug release from block copolymers were developed at pH 7.4 and 5.0 of two periods (stage I: 0~12 h, stage II: 12~96 h). RESULTS: The models built are of good fitting ability, internal predictive ability, stability and statistically significance. Drug diffusion is mainly influenced by the intra-block force, and micellar erosion by inter-block force. At pH 5.0, lowest unoccupied molecular orbital energy of copolymer unit is the main factor influencing the En. Stage I of drug release is affected by hydrophobic property and stage II by regional polar of copolymer molecules. CONCLUSION: The models present good performance, factors affecting drug release behavior at different pH conditions can offer guidance for the design of copolymer structures to control the drug release behavior of micelles in a targeted and quantitatively way.