Structural Effects of Dibucaine Encapsulation into Solid Lipid Nanoparticles and Nanostructured Lipid Carriers

Abstract

Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) are innovative alternatives in nanoencapsulation with a wide potential for controlled drug release. Dibucaine (DBC) is a potent long-acting local anesthetics but it is also toxic to the central nervous system. The purpose of this work was to produce SLN and NLC formulations at pH 7.4 - composed by myristyl myristate (MM) or MM / myglyol® in their lipid matrices, respectively, plus Pluronic F68 - for DBC delivery, aiming a future application for pain control in the skin. The lipid particles were characterized by nanoparticle tracking analysis (NTA) and electron paramagnetic resonance (EPR) with nitroxide spin probes. The size of SLN and NLC loaded with DBC were 175.67±10.69 and 170.67± 3.79nm, respectively; no significant changes were detected after DBC addition (p ≤ 0.05, unpaired t-test). Size distribution, given by the Span value, was kept below 1, as expected for homogeneous dispersed colloids. EPR spectra of nitroxide probes revealed that dibucaine insertion into the nanoparticles below the fusion temperature of MM increased lipid packing (ιh+1/h0 height ratio) while the opposite (ηh+1/h0) occurs at 55oC. Moreover, the partition of DBC into SLN/NLC seems to be a stable process since no hysteresis was observed after a few heating/cooling cycles. In conclusion, we successfully prepared SLN and NLC particles containing DBC which, in turn affects their structural properties. Supported by FAPESP (# 06/00121-9) and CAPES (Brazil).