Drugs/lamellae interface influences the inner structure of double-loaded liposomes for inhaled anti-TB therapy: An in-depth small-angle neutron scattering investigation

With the aim of developing new drug carriers for inhalation therapy, we report here an in depth investigation
of the structure of multilamellar liposomes loaded with two well-established anti-tubercular (anti-TB) drugs,
isoniazid (INH) and rifampicin (RIF), by means of small-angle neutron-scattering (SANS) analysis. Unloaded,
single drug-loaded and co-loaded liposomes were prepared using different amounts of drugs and characterized
regarding size, encapsulation efficiency and drug release. Detailed information on relevant properties of the
investigated host-guest structures, namely the steric bilayer thickness, particle dispersion, number of lamellae
and drug localization was studied by SANS. Results showed that RIF-liposomes were less ordered than unloaded
liposomes. INH induced a change in the inter-bilayer periodical spacing, while RIF-INH co-loading
stabilized the multilamellar liposome architecture, as confirmed by the increment of the drug loading capacity.
These findings could be useful for the understanding of in vitro and in vivo behavior of these systems and for
the design of new drug carriers, intended for inhaled therapy.