Influence of amino acids on the aggregation behavior and drug solubilization of branched block copolymers

Abstract

Block copolymers and their related structure-performance relationships for controllable drug delivery have gained much attention recently. In this work, multibranched PEO-PPO copolymer M904 was synthesized, which had the same PEO and PPO segments with commercial 4-branched copolymer Tetronic 904 (T904). The effect of three amino acids alkaline lysine (Lys), neutral glycine (Gly) and acidic glutamic acid (Glu) on the aggregation behavior of M904 and T904 were investigated. The solubilization and in vitro release property of hydrophobic drug simvastatin (ST) were estimated. Compared to T904, lower cloud point, bigger critical aggregation concentration (CAC), smaller micropolarity, larger size aggregates, better drug solubilization capacity and drug released at a slower rate were features of multibranched copolymer M904. With the addition of Lys or Gly, cloud point, micropolarity and CAC decreased, while aggregates size and drug solubility raised, the rate of drug release slowed, and Lys had a greater effect than Gly. Glu showed opposite behavior, CAC and cloud point increased, and release rate became faster. Both the alteration of copolymer architecture and the addition of amino acids could regulate the copolymer performance, which would be beneficial to design drug formulations in pharmaceutical applications.