Effect of Lipophilicity of Dispersed Drugs on the Physicochemical and Technological Properties of Solid Lipid Nanoparticles

Abstract

A series of aliphatic esters of the NSAID naproxen (NAP) were synthesised and encapsulated in solid lipid nanoparticles (SLN) to evaluate the influence of lipophilicity on drug loading and release, as well as physicochemical properties and stability of SLN. The lipophilicity of esters mainly showed to influence their affinity for the solid lipid matrix, modifying the drug release profile compared to the parent drug, whereas drug encapsulation efficiency and the technological properties and stability of SLN were not affected. After storage at room temperature the in vitro release profiles of esters changed with respect to freshly prepared systems, depending on the lipophilicity of the dispersed derivative. In particular, the SLN containing the medium-chain hexyl and octyl esters showed a 70-80% increase of drug release after storage; SLN loaded with NAP or the lower ethyl and butyl esters did not show significant changes in the drug release rate. Such findings reveal that the affinity of NAP esters for the lipid network of the nanoparticles is strongly dependent on their lipophilicity and an excessive increase of the latter negatively influences the allocation and retention on these com- pounds in the nanoparticles.