Characterization of lyotropic liquid systems loaded with Gold(I) phosphane compounds for anticancer drug delivery

Characterization of lyotropic liquid systems loaded with Gold(I) phosphane compounds for anticancer drug delivery Michela Pisani1, Rossana Galassi2, Paola Astolfi1, Elisabetta Giorgini3, Barbara Rossi4, Francesco D’Amico4 - 1. Dipartimento SIMAU, Università Politecnica delle Marche, Via Brecce Bianche, Ancona, I-60131. 2. Scuola di Scienze e Tecnologie, Divisione Chimica, Università di Camerino, Via Sant’Agostino, I-62032. 3. Dipartimeto DiSVA, Università Politecnica delle Marche, Via Brecce Bianche, Ancona, I-60131. 4. Elettra - Sincrotrone Trieste S.C.p.A., S.S. 14 - km 163.5, Basovizza, Trieste, I-34149. A continuous research effort for the production of efficient nanocarriers for drug delivery in anticancer therapy is in progress in order to develop formulations with higher degree of specificity and reduced adverse effects. In particular, liquid crystalline phases such as cubosomes and hexosomes represent interesting drug delivery matrixes.1,2 The properties of the hexosomes and cubosomes, such as size, structure, and stability, can be tuned by their internal composition, polymer concentration, and processing conditions. Moreover, the stiffness of these phases could lead to a slower diffusion of the solubilized cargo and hence to a long-term release. Within this frame, we are currently developing bio-systems based on hexagonal and cubic phases dispersed in a continuous aqueous medium, which could find potential application as anticancer drug delivery vectors. In particular, phytantriol cubic phases have been used to encapsulate both commercial (5-fluororuracil)3 and non commercial chemotherapy drugs such as Gold(I) phosphane complexes. These latter compounds have shown to possess anti-neoplastic effects on many cancer cell panels4 and unique in vitro ability to induce a dose-dependent inhibition of cell proliferation in both BLBC murine A17 and human MDA-MB-231 cells. Therefore, ((triphenylphosphine)-gold(I)-(4,5-dichloroimidazolyl-1H-1yl)) (CS 47) and ((triphenylphosphine)-gold(I)-(4,5-dicyanoimidazolyl-1H-1yl)) (DM20) have been encapsulated in different lipid matrix such as phytantriol, DOPE and monoolein. An integrated experimental approach involving X-ray diffraction, ATR-FTIR and UV Resonant Raman spectroscopies has been employed to establish the effects of drug encapsulation on the structure and phase behavior of the mesophases. In particular, SAXS diffraction experiments have been carried out to investigate the lipid nanostructure and the possible geometrical and topological modifications induced by encapsulation of gold complexes. Additional information at molecular level on the interaction between such complexes and lipid matrix has been obtained by means of ATR-FTIR and UV-Resonant Raman spectroscopy. This study represents an important turning point in Gold(I) bioinorganics. In fact, the encapsulation should prevent the exchange reactions usually occurring with the cysteine groups of serum albumin, leading to a systemic toxicity with homeostatic effects.5 References 1. Angelova, A.; Angelov, B.; Mutafchieva, R.; Lesieur, S.; Couvreur, P. Self-Assembled Multiconmpartment Liquid Crystalline Lipid Carriers for Protein, Peptide, and Nucleic Acid Drug Delivery. Acc. Chem. Res. 2011, 44 (2), 147-156. 2. Conn, C. E.; Drummond, C. J. Nanostructured bicontinuos cubic lipid self-assembly materials as matrices for protein encapsulation. Soft Matter 2013, 9, 3449-3464. 3. Astolfi, P.; Giorgini, E., Gambini, V., Rossi, B., Vaccari, L., Vita, F., Francescangeli, O., Marchini, C., Pisani, M. Lyotropic Liquid-Crystalline Nanosystems as Drug Delivery Agents for 5‑Fluorouracil: Structure and Cytotoxicity. Langmuir 2017, 33,12369-12378. 4. Galassi R. et al. Dalton Transactions, 2012, 41, 5307-5318. 5. Bhabak K. B. et al., Dalton Trans., 2011, 40, 2099-2111.