DEVELOPMENT AND COMPARISON OF TWO LIPID-BASED NANOSYSTEMS FOR THE CO-DELIVERY OF RIFAMPICIN AND ISONIAZID: SMALL-ANGLE NEUTRON SCATTERING CHARACTERISATION

Recently lipid-based drug delivery system (DDS), such as Solid Lipid Nanoparticles (SLNs) and liposomes, have been proposed in the inhaled therapy to improve the drug targeting and delivery. In this work SLNs and liposomes were studied for the co-delivery of two first-line anti-tuberculosis drugs, Rifampicin (RIF) and Isoniazid (INH). RIF and INH were chosen as model drugs, since they display different physicochemical features: RIF is a poor water soluble compound, while INH is extremely hydrophilic. Both lipid-based DDS (SLN and liposomes) have been characterized regarding size and zeta potential by DSL (dynamic light scattering) and regarding shape and external morphology by AFM (atomic force microscopy) and by SEM (scanning electron microscopy). Moreover, drug content, in vitro drug release and stability in suspension, were evaluated in order to highlight the effects of the co-encapsulation. In fact, drugs can interact with the delivery systems modifying its properties and in vitro behaviour. In order to comprehend and evaluate the possible interactions between drugs and DDS, loaded SLNs and liposomes has been further studied by small-angle neutron scattering (SANS). Small-Angle Neutron Scattering (SANS) is a useful tool in gaining a detailed understanding of the structure of macromolecular systems that make up SLN and liposomes. SANS is widely applicable, with the inherent advantage over visual techniques, of probing accurately structural features on nanometer length scales as well as yielding ensemble-averaged information on freely water-suspended membranes. Of note, the SANS D2O/H2O contrast variation methodology allows a well distinguished scattering from the shell with respect to the corresponding inner content. Besides, SANS do not entail the addition or inclusion of bulky fluorescent dyes or labels needed by other techniques (i.e. fluorescence and electron microscopy), which can perturb or affect the phase behavior observed.