Kaassis, Abdessamad; (2016) Low-dimensional matrices for the delivery of pharmaceutically active agents. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

When an active pharmaceutical ingredient (API) is encapsulated within, or attached to, a carrier, drug safety and efficacy can be considerably increased and new therapies are possible. In this work, two different types of low-dimensional carriers have been explored as potential advanced drug delivery systems. These comprise polymer nanofibers, a type of 1D-system, and two 2D systems: layered double hydroxides (LDHs) and hydroxy double salts (HDSs). Three types of nanofibers were initially produced by electrospinning: polyvinylpyrrolidone (PVP)/sodium ibuprofen (SI), PVP/sodium alginate (SA)/SI and poly(ethylene oxide) (PEO)/SA/SI. The fibers were characterized by X-ray diffraction (XRD), nuclear magnetic resonance (NMR), and Fourier transform infrared spectroscopy (FTIR), and drug release explored. The PEO/SA/SI fibers showed interesting pulsatile release charactersitics, and thus additional fibers containing PEO/SA and other drugs (sodium valproate, diclofenac, and naproxen) were produced and investigated. The sodium salts of diclofenac, naproxen and valproic acid were also successfully intercalated into known Zn-containing HDS materials by ion-exchange intercalation. The products were characterised by XRD, FTIR, and NMR. The intercalation processes were studied using in situ X-ray diffraction, and drug release studies were undertaken. The release timescale is potentially useful for commercial applications, but the amount of Zn and (in some cases) the presence of Co and Ni in the materials is potentially a concern. Thus, new biocompatible HDSs containing Zn, Mg and Fe were prepared and loaded with drugs. Drug release was investigated, and the new HDSs were formulated into tablets. The latter were subject to the standard pharmacopoeial tests. Finally, LDHs were explored. Phosphonoacetic and sulfoacetic acid were successfully intercalated, and the products characterised by XRD, FTIR, and NMR. The intercalation process was probed using in situ XRD, and interesting intermediate phases observed. Molecular modelling was used to explore these systems, and drug release investigated.

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