How Molecular Mobility, Physical State, and Drug Distribution Influence the Naproxen Release Profile from Different Mesoporous Silica Matrices

abstract

Aiming to evaluate how the release profile of naproxen (nap) is influenced by its physical state, molecular mobility, and distribution in the host, this pharmaceutical drug was loaded in three different mesoporous silicas differing in their architecture and surface composition. Unmodified and partially silylated MCM-41 matrices, respectively MCM-41 and MCM-41(sil), and a biphenylene-bridged periodic mesoporous organic matrix, PMOBph, were synthetized and used as drug carriers, having comparable pore sizes (similar to 3 nm) and loading percentages (similar to 30% w/w). The loaded guest was investigated by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and dielectric relaxation spectroscopy (DRS). DSC and XRD confirmed amorphization of a nap fraction incorporated inside the pores. A narrower glass transition was detected for PMOBph_nap, taken as an indication of the impact of host ordering, which also hinders the guest molecular mobility inside the pores as probed by DRS. While the PMOBph matrix is highly hydrophobic, the unmodified MCM-41 readily adsorbs water, accelerating the nap relaxation rate in the respective composite. In the dehydrated state, the faster dynamics was found for the silylated matrix since guest-host hydrogen bond interactions were inhibited to some extent by methylation. Nevertheless, in all the prepared composites, bulk-like crystalline drug deposits outside pores in a greater extent in PMOBph_nap. The DRS measurements analyzed in terms of conductivity show that, upon melting, nap easily migrates into pores in MCM-41-based composites, while it stays in the outer surface in the ordered PMOBph, determining a faster nap delivery from the latter matrix. On the other side, the mobility enhancement in the hydrated state controls the drug delivery in the unmodified MCM-41 matrix vs the silylated one. Therefore, DRS proved to be a suitable technique to disclose the influence of the ordering of the host surface and its chemical modification on the guest behavior, and, through conductivity depletion, it provides a mean to monitor the guest entrance inside the pores, easily followed even by untrained spectroscopists.

subject category

Medicine, Research & Experimental; Pharmacology & Pharmacy

authors

d'Orey, P; Cordeiro, T; Lourenco, MAO; Matos, I; Danede, F; Sotomayor, JC; Fonseca, IM; Ferreira, P; Correia, NT; Dionisio, M

Groups

G1 - Porous Materials and Nanosystems
G2 - Photonic, Electronic and Magnetic Materials

Projects

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

Projeto de Investigação Exploratória: Paula Ferreira (IF_Paula Ferreira)

acknowledgements

This work was supported by the Associate Laboratory for Green Chemistry LAQV, which is financed by national funds from FCT/MEC (UID/QUI/50006/2019) and CICECOAveiro Institute of Materials (UIDB/50011/2020 & UIDP/50011/2020 (CICECO)) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER 007265). This work has received funding from the Interreg 2 Seas program 2014-2020 co-funded by the European Regional Development Fund (FEDER) under subsidy contract 2S01059_IMODE. T.C. acknowledges Fundacao para a Cie<^>ncia e a Tecnologia (FCT) for the scholarship SFRH/BD/114653/2016. I.M. acknowledges FCT for the Investigador FCT contract IF/01242/2014/CP1224/CT0008. P.F. acknowledges the grant IF/00300/2015. Nitrogen absorption analysis was obtained at Laborato ' rio de Ana ' lises/Requimte of the Chemistry Department-Universidade Nova de Lisboa.