Slightly viscous oxidized alginate dispersions as vehicles for intranasal administration of the α-synuclein aggregation inhibitor Anle 138b in free form or encapsulated in solid lipid nanoparticles

Abstract

The aim of the present work was to evaluate the performance of slightly viscous dispersions (SVDs) of the mucoadhesive oxidized alginate (Alg OX) with or without hydroxypropylmethyl cellulose (HPMC) as vehicles for brain delivery of the α-synuclein aggregation inhibitor Anle 138b loaded solid lipid nanoparticles (Anle 138b SLNs) by intranasal administration. For this purpose, the required Anle 138b loaded SLNs were prepared employing the self-emulsifying Gelucire® 50/13 as lipid matrix following the melt emulsification method. The resulting nanocarriers showed a mean diameter of 99 ± 3 nm, an average zeta potential of −5.0 ± 0.2 mV and the encapsulation efficiency of 65 ± 2 %. Their stability on storage was found of a month at 4 °C and 24 h at 37 °C. Solid state studies on Anle 138b SLNs, based on FT-IR and Raman at mid- and at higher-frequency spectra, suggested that the inhibitor is endowed with higher fluidity compared to the pure drug and X-ray diffraction spectra allowed us to assess the reduced crystallinity state for Anle 138b SLNs. The Alg OX based SVDs were prepared by aqueous dispersion of mucoadhesive polymer at low concentrations to which SLN pellets were added. Drug release studies employing SVDs and SNF/mucin mixture as release medium showed quantitative release of the inhibitor within 48 h. We conclude that Anle 138b SLN Alg OX/HPMC SVD constitutes a promising formulation due to its capability to provide the inhibitor in quantitative and sustained way, being not cytotoxic towards human RPMI 2650 cells and neuronal SH-SY5Y cells.