Synthesis and Characterization of LDN-57444 Loaded Polymeric Micelles

The amphiphilic triblock copolymer [P(MeOx₃₇-b-PBuOx₂₁-b-PMeOx₃₆)), Mn = 8.25 kg/mol, PDI (DM = 1.21)] was synthesized as reported previously by using living cationic ring-opening polymerization and used to prepare LDN-57444 loaded polymeric micelle formulation (LDN-POx) via the thin film hydration method [39 (link)]. Briefly, predetermined amounts of polymer and LDN-57444 were each dissolved in organic solvents and mixed together. The organic solvent was then evaporated under a stream of nitrogen gas (50 °C) to form the thin film. To completely remove the residual organic solvent, the films were deposited in the vacuum chamber (approx. 0.2 mbar) overnight. Subsequently, the thin films were rehydrated with saline and then incubated at room temperature for 10 min to produce LDN-57444 loaded polymeric micelle formulations. The aqueous polymeric micelle formulation was centrifuged at 10,000 rpm for 3 min (Sorvall Legend Micro 21R Centrifuge, Thermo Scientific) to precipitate non-dissolved drug or drug-polymer aggregates. The transparent supernatant solutions of micelle samples were used for the further analysis. The hydrodynamic diameter and polydispersity index (PDI) of LDN-57444 loaded polymeric micelles were determined by dynamic light scattering (DLS) using Malvern Nanosizer.