Flexibility and drug release features of lipid/saccharide nanoparticles

Abstract

The effect of lipophilic additives (excipients and drugs) on the behavior of lipid/saccharide nanoparticles has been investigated by incoherent elastic neutron scattering. Temperature scans from 20 K to 350 K have been performed on lecithin/chitosan particles loaded with isopropyl myristate and cetyl-stearyl alcohol, two lipophilic molecules with different melting temperatures which are commonly added to improve drug loading efficiency. In a similar way the effect of tamoxifen citrate, a lipophilic drug frequently used in breast cancer therapy, has also been studied. The different melting points of the two excipients affect mostly the low-temperature behavior of the nanoparticles. At physiological temperatures they both improve the particle flexibility. On the other hand addition of tamoxifen leads to stiffer structures and to lower amounts of released drug. The macroscopic features of the drug release appear to be correlated to the microscopic flexibility determined by neutron scattering. The data confirm also the role of chitosan as a stiffening and stabilizing agent of the lipid particles.