title: Reverse Microemulsion-Based Synthesis of (Bis)phosphonate-Metal Materials with Controllable Physical Properties: An Example Using Zoledronic Acid-Calcium Complexes.
abstract: The development of phosphonate-metal materials is tightly related to the advancement in their synthesis methods. Herein, using zoledronic acid (Zol), a bisphosphonate (bioacitve phosphonate with a "P-C-P" structure), and calcium as model molecules, we applied the reverse microemulsion (RM) method to synthesize a series of Zol-Ca complexes. We comprehensively (i) studied the relationship between RM conditions, including the component ratio of RM, cosurfactants, reaction time, reactant concentration, reaction temperature, and the presence of a phospholipid, 1, 2-dioleoyl-sn-glycero-3-phosphate acid (DOPA), and the physical properties of the complexes synthesized (i.e., shape, size, uniformity, monodispersity, and hydrophilicity/hydrophobicity) and (ii) explored the underlying mechanisms. To evaluate the biomedical application potential of the Zol-Ca complexes synthesized, one type of hydrophobic, DOPA-coated spherical Zol-Ca complexes (denoted as Zol-Ca@DOPA) was formulated into a PEGylated lipid-based nanoparticle formulation (i.e., Zol-Ca@bilipid NPs, ∼24 nm in diameter). In a mouse model with orthotopic mammary tumors, the Zol-Ca@bilipid NPs significantly enhanced the distribution of Zol in tumors, as compared to free Zol. It is expected that the RM-based synthesis of (bis)phosphonate-metal materials with controllable physical properties will help expand their applications.
authors.affiliation: The University of Texas at Austin , College of Pharmacy, Division of Pharmaceutics, Austin, Texas 78712, United States.
authors.forename: Xu
authors.identifier: http://orcid.org/0000-0002-6168-2442
authors.initials: X
authors.lastname: Li
authors.affiliation: The University of Texas at Austin , College of Pharmacy, Division of Pharmaceutics, Austin, Texas 78712, United States.
authors.forename: Youssef W
authors.identifier: http://orcid.org/0000-0002-3686-8392
authors.initials: YW
authors.lastname: Naguib
authors.affiliation: The University of Texas at Austin , College of Pharmacy, Division of Pharmaceutics, Austin, Texas 78712, United States.
authors.forename: Solange
authors.initials: S
authors.lastname: Valdes
authors.affiliation: The University of Texas at Austin , College of Pharmacy, Division of Pharmaceutics, Austin, Texas 78712, United States.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hufnagel
authors.affiliation: The University of Texas at Austin , College of Pharmacy, Division of Pharmaceutics, Austin, Texas 78712, United States.
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Cui
keywords: distribtuion in tumor; formation mechanism; macrophages; microemulsion compositions; nanoparticles; reaction conditions