Polymorphic Transformation of Drugs Induced by Glycopolymeric Vesicles Designed for Anticancer Therapy Probed by Solid-State NMR Spectroscopy

0508836 - ÚOCHB 2020 RIV US eng J - Journal Article
Procházková, Eliška - Cao, C. - Rawal, A. - Dračínský, Martin - Bhattacharyya, S. - Císařová, I. - Hook, J. M. - Stenzel, M. H.
Polymorphic Transformation of Drugs Induced by Glycopolymeric Vesicles Designed for Anticancer Therapy Probed by Solid-State NMR Spectroscopy.
ACS Applied Materials and Interfaces. Roč. 11, č. 31 (2019), s. 28278-28288. ISSN 1944-8244. E-ISSN 1944-8252
Grant - others:AV ČR(CZ) MSM200551801
Program: Program na podporu mezinárodní spolupráce začínajících výzkumných pracovníků
Institutional support: RVO:61388963
Keywords : CASTEP calculations * drug delivery * ellipticine * glycopolymeric vesicles * polymorphism * solid-state NMR * XRD
OECD category: Physical chemistry
Impact factor: 8.758, year: 2019
Method of publishing: Limited access
https://pubs.acs.org/doi/10.1021/acsami.9b05514

Understanding the nature of the drug-polymer interactions in micellar drug delivery systems and what happens with the drug and the polymer once the complex has formed is essential for the rational design of the polymeric matrices suitable for a particular drug. In this work, glycopolymeric vesicles-a block copolymer, poly(1-O-methacryloyl-beta-D-fructopyranose)-b-poly(methyl methacrylate), (PFru(36)-PMMA(160)), -designed to target tumor cells loaded with two drugs, ellipticine and curcumin, were characterized. Advanced solid-state NMR spectroscopy and single-crystal/powder X-ray diffraction (XRD) combined with CASTEP calculations shed light on the nature of the drug, the polymer, and their interactions. While the low drug loading (ca. 5%) ensured that the structure, size, and shape of the polymeric vesicles did not change significantly, the solid-state forms of the drugs changed markedly. Upon loading into the vesicles, ellipticine favored a highly ordered form distinctly different from the bulk drug as indicated by C-13 solid-state NMR spectroscopy. A detailed analysis of the CASTEP-calculated C-13 spectra derived from crystallographic data based on the lowest mean absolute error showed the best match with form I. Moreover, ellipticine before loading was found as a new polymorph and was described by single-crystal XRD as a new orthorhombic Form III. Likewise, curcumin, originally present in monoclinic Form I was found to recrystallize as metastable orthorhombic Form II inside the vesicles. Intermolecular interactions between the polymeric vesicles and the drugs, ellipticine as well as curcumin, were detected using 2D H-1 magic angle spinning experiments, indicating that the drugs are localized in the hydrophobic layer of the vesicles.
Permanent Link: http://hdl.handle.net/11104/0299639