Antimicrobial Activity from Colistin-Heparin Lamellar-Phase Complexes for the Coating of Biomedical Devices

Infections arising in hospitalized patients, particularly those who have undergone surgery and are reliant on receiving treatment through biomedical devices, continue to be a rising concern. It is well-known that aqueous mixtures of oppositely charged surfactant and polymer molecules can self-assemble to form liquid crystalline structures, primarily via electrostatically driven interactions that have demonstrated great potential as tailored-release nanomaterials. Colistin is a re-emerging antibiotic used against multidrug-resistant Gram-negative bacteria. Its amphiphilic structure allows it to form micellar aggregates in solution. Thus, the aim of this study was to determine whether structured complexes form between colistin and negatively charged biopolymers, such as the highly sulfated anticoagulant, heparin. Cross-polarized light microscopy and synchrotron small-angle X-ray scattering were employed to visualize the appearance of birefringent structures and identify liquid crystalline structures, respectively, formed across the interface between solutions of colistin and heparin. A lamellar phase with a lattice parameter of ∼40 Å was formed upon contact between the oppositely charged solutions of colistin and heparin. In addition, in vitro release studies showed a slow release of colistin from the lamellar-phase gel complexes into the bulk media, and disk diffusion bioassays revealed antimicrobial activity against Pseudomonas aeruginosa. This system provides a novel, cost-effective, and simple approach to reducing the risk of infections by potentially applying the formulation as a coating for biomedical implants or tubing.