Design and evaluation of nanostructured lipid carriers loaded with Salvia officinalis extract for Alzheimer's disease treatment

Abstract

Considering the potential of Salvia officinalis in prevention and treatment of Alzheimer's disease (AD), as well as the ability of nanostructured lipid carriers (NLC) to successfully deliver drug molecules across blood–brain barrier (BBB), the objective of this study was design, development, optimization and characterization of freeze‐dried salvia officinalis extract (FSE) loaded NLC intended for intranasal administration. NLC were prepared by solvent evaporation method and the optimization was carried out using central composite design (CCD) of experiments. Further, the optimized formulation (NLCo) was coated either with chitosan (NLCc) or poloxamer (NLCp). Surface characterization of the particles demonstrated a spherical shape with smooth exterior. Particle size of optimal formulations after 0.45 μm pore size filtration ranged from 127 ± 0.68 nm to 140 ± 0.74 nm. The zeta potential was −25.6 ± 0.404 mV; 22.4 ± 1.106 mV and − 6.74 ± 0.609 mV for NLCo, NLCc, and NLCp, respectively. Differential scanning calorimetry (DSC) confirmed the formation of NLC whereas Fourier‐transform infrared spectroscopy confirmed the FSE encapsulation into particles. All formulations showcased relatively high drug loading (>86.74 mcg FSE/mg solid lipid) and were characterized by prolonged and controlled release that followed Peppas‐Sahlin in vitro release kinetic model. Protein adsorption studies revealed the lowest adsorption of the proteins onto NLCp (43.53 ± 0.07%) and highest protein adsorption onto NLCc (55.97 ± 0.75%) surface. The modified ORAC assay demonstrated higher antioxidative activity for NLCo (95.31 ± 1.86%) and NLCc (97.76 ± 4.00%) as compared to FSE (90.30 ± 1.53%). Results obtained from cell cultures tests pointed to the potential of prepared NLCs for FSE brain targeting and controlled release.

Comparative Studies of the Uptake and Internalization Pathways of Different Lipid Nano-Systems Intended for Brain Delivery

“…The presence of poloxamer 407 in the NLPOL formulation was confirmed by the band at 841 cm −1 and was assigned to the PEO chain of the poloxamer [ 31 ]. This spectral window in the formulation was not interfered with by any other band of the other excipients [ 32 ].…”

“…Moreover, the spectra of the two aforementioned components differed in the position of the C=O carbonyl stretching vibration at 1727 cm −1 (ester group) in the phospholipon and 1710 cm −1 (carboxyl group) in the oleic acid. However, broader bands in this region are seen in the spectra of the NLC formulations (1738 cm −1 and 1735 cm −1 for NLCPEG and NLCPOL, respectively), which could be explained by the overlap of the discussed carboxyl stretching bands [ 32 ]. The presence of DSPE-mPEG 2000 in the NLCPEG and poloxamer 407 in the NLCPOL could be confirmed by the weak bands at 1115 cm −1 and 1061 cm −1 in the NLCPEG and 1144 cm −1 in the NLCPOL (upper band from the C–O and lower band from the C–C stretching vibrations).…”

Solid Lipid Nanoparticles: A Nano Drug Carrying System in Treatment of Nervous Diseases

“…Therefore, to improve the applicability of ropinirole in alleviating syndromes of PD, the effort to increase its pharmacokinetics and pharmacodynamics is required. Considering the advantages of using SLNs, Narendar et al designed, optimized and evaluated ropinirole loaded SLNs [31], and hydrogel containing ropinirole loaded SLNs formulations, finding that RP-loaded SLNs and RPloaded SLNs hydrogels have better permeations and drug release stability compared with conventional formulations. For the pharmacokinetics evaluation, the enhancement factor of hydrogel containing SLNs is 3.0 which is better than that of hydrogel-free SLNs with a factor of 2.1.…”