title: Lipocalin-2-loaded amphiphilic polyanhydride microparticles accelerate cell migration.
abstract: This work demonstrates that amphiphilic polyanhydride microparticles based on co-polymers of 1,6-bis(p-carboxyphenoxy)hexane (CPH) and 1,6-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) provide stabilizing environments for proteins. A cryogenic atomization method was used to fabricate protein-loaded polyanhydride microparticles. These microparticles were tested for their ability to provide controlled delivery of lipocalin 2 (Lcn2) and to maintain its structure and function. Lcn2 is an acute-phase protein suspected to play a role in cell migration and tissue repair. The in vitro release kinetics of Lcn2 from the microparticles were a function of the chemistry of the polymer carrier. The biological activity of Lcn2 released from polyanhydride microparticles was investigated by its ability to stimulate migration of human colon epithelial cells (HCT116). Lcn2 released from 50:50 and 20:80 CPTEG/CPH microparticles maintained its biological activity as demonstrated by the increased rate of cell migration. In addition, the Lcn2-loaded 50:50 and 20:80 CPTEG/CPH microparticles promoted cell migration over that of the Lcn2 administered alone. This was interpreted as the ability of the amphiphilic microparticles to stabilize the encapsulated protein and release it in a controlled manner over a period of time. This work demonstrates the potential for therapeutic use of amphiphilic polyanhydride microparticles as protein/drug carriers.
authors.affiliation: a Department of Chemical and Biological Engineering, Iowa State University, 2035 Sweeney Hall, Ames, IA 50011, USA.
authors.forename: Latrisha K
authors.initials: LK
authors.lastname: Petersen
authors.forename: Amy S
authors.initials: AS
authors.lastname: Determan
authors.forename: Christine
authors.initials: C
authors.lastname: Westgate
authors.forename: Lee
authors.initials: L
authors.lastname: Bendickson
authors.forename: Marit
authors.initials: M
authors.lastname: Nilsen-Hamilton
authors.forename: Balaji
authors.initials: B
authors.lastname: Narasimhan
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D016503:Drug Delivery Systems / Q000295:instrumentation; D004591:Electrophoresis, Polyacrylamide Gel; D045325:HCT116 Cells; D006586:Hexanes / Q000737:chemistry; D006801:Humans; D054834:Lipocalins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008855:Microscopy, Electron, Scanning; D049388:Polyanhydrides / Q000737:chemistry; D020011:Protective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013501:Surface-Active Agents / Q000737:chemistry; D014945:Wound Healing / Q000187:drug effects
chemical_list: C120991:1,6-bis(carboxyphenoxy)hexane; D006586:Hexanes; D054834:Lipocalins; D049388:Polyanhydrides; D020011:Protective Agents; D013501:Surface-Active Agents