A prospective class of materials for drug delivery is lyotropic liquid crystalline (LLC) nanoparticles, such as cubosomes and hexosomes. Efforts are being made to generate a pH dependent system, which exhibits slow release hexosomes (H-2) at physiological pH and relatively fast release cubosomes (Q(2)) at acidic disease sites such as in various cancers and bacterial infection (pH similar to 5.5-6.5). Herein, we report the synthesis of nine ionizable aminolipids, which were doped into monoolein (MO) lipid nanoparticles. Using high throughput formulation and synchrotron small angle X-ray scattering (SAXS), the effects of aminolipid structure and concentration on the mesophase of MO nanoparticles at various pHs were determined. As the pH changed from neutral to acidic, mesophases, could be formed in an order L-2 (inverse micelles) -> H-2 -> Q(2). Specifically, systems with heterocyclic oleates exhibited the H-2 to Q(2) transition at pH 5.5-6.5. Furthermore, the phase transition pH could be fine-tuned by incorporating two aminolipids into the nanoparticles. Nanoparticles with a pH dependent phase transition as described in this study may be useful as drug delivery carriers for the treatment of cancers and certain bacterial infection. (C) 2020 Elsevier Inc. All rights reserved.