Phase behavior of the quaternary poly(DL-lactide-co-glycolide)/monoolein/1-methyl-2-pyrrolidinone/water system: An experimental and theoretical study

The phase behavior of the poly(DL-lactide-co-glycolide) (PLG)/monoolein (MO )/1-methyl-2-pyrrolidinone (NMP)/water system has been studied. The particu lar system was selected because it was a candidate for being a suitable sys tem for creation of lipid-polymer hybrid particles. Phase diagrams of the f our ternary subsystems, as well as phase behaviors of selected quaternary m ixtures, have been determined. The PLG/ NMP/water system exhibits a behavio r similar to a polymer/solvent/nonsolvent system, and the PLG/MO/ NMP syste m shows a segregative behavior similar to a polymer 1/polymer 2 (or surfact ant)/solvent system. The ternary MO/NMP/water subsystem exhibits a rich, ma inly mesomorphic phase behavior, including lamellar and cubic phases, and o ffers thus possibilities to create both liposomes and cubosomes. At high NM P content, the system gives rise to several liquid phases, such as a sponge phase and MO-poor and MO-rich liquid phases. Addition of PLG to the MO/NMP /water subsystem reveals that both liquid crystals and liquid phases may ex ist in equilibrium with PLG-rich liquids, the latter being highly viscous. At high water content, the PLG phase may be caught in a glassy state at roo m temperature. The Flory-Huggins theory has been used to model three of the ternary subsystems and some parts of the quaternary system.