Nose-to-brain delivery of self-assembled curcumin-lactoferrin nanoparticles: Characterization, neuroprotective effect and in vivo pharmacokinetic study

Abstract

Curcumin (CUR) is a natural polyphenol extract with significant antioxidant and anti-inflammatory effects, which indicates its great potential for neuroprotection. Lactoferrin (LF), a commonly used oral carrier and targeting ligand, has not been reported as a multifunctional nanocarrier for nose-to-brain delivery. This study aims to develop a nose-to-brain delivery system of curcumin-lactoferrin nanoparticles (CUR-LF NPs) and to further evaluate the neuroprotective effects in vitro and brain accumulation in vivo. Herein, CUR-LF NPs were prepared by the desolvation method with a particle size of 84.8 ± 6.5 nm and a zeta potential of +22.8 ± 4.3 mV. The permeability coefficient of CUR-LF NPs (4.36 ± 0.79 × 10−6 cm/s) was 50 times higher than that of CUR suspension (0.09 ± 0.04 × 10−6 cm/s) on MDCK monolayer, indicating that the nanoparticles could improve the absorption efficiency of CUR in the nasal cavity. Moreover, CUR-LF NPs showed excellent protection against Aβ25-35-induced nerve damage in PC12 cells. In vivo pharmacokinetic studies showed that the brain-targeting efficiency of CUR-LF NPs via IN administration was 248.1%, and the nose-to-brain direct transport percentage was 59.7%. Collectively, nose-to-brain delivery of CUR-LF NPs is capable of achieving superior brain enrichment and potential neuroprotective effects.

KLVFF Conjugated Curcumin Microemulsion-Based Hydrogel for Transnasal Route: Formulation Development, Optimization, Physicochemical Characterization, and Ex Vivo Evaluation

“…In addition, Zang et al formulated a curcumin/hydroxypropyl-β-cyclodextrin inclusion complex and reported that the plasma and brain concentrations of the formulation were higher than those in the control group after intranasal administration [ 69 ]. Moreover, Li et al reported that curcumin-lactoferrin nanoparticles demonstrated excellent brain accumulation, prolonged elimination half-life, and improved bioavailability of curcumin after intranasal administration [ 70 ]. Based on this information, it indicates the strong performance of nanoformulations to improve the pharmacokinetics and efficacy of curcumin.…”

Research progress in brain-targeted nasal drug delivery

“…To increase the nose-to-brain delivery of nanoscale drugs, selecting appropriate ligands for surface modification of the formulation can increase the affinity between the drug delivery system and the mucosa, leading to enhanced mucosal adsorption. The most commonly used targeting ligands are proteins whose receptors are expressed in the olfactory region, namely lactoferrin ( Li et al, 2023 ) or certain glycoproteins ( Pernet et al, 2023 ). Several lectins, such as wheat germ agglutinin ( Su et al, 2020 ) and solanum tuberosum lectin ( Chen et al, 2012 ), have also been used to promote nose-to-brain drug delivery.…”

Nose‐to‐brain delivery of nanotherapeutics: Transport mechanisms and applications

“…Pure lactoferrin can also, through self-assembly, combine with small molecule drugs to form nanoscale formulations suitable for intranasal administration. Lf and curcumin nanoparticles prepared by desolvation for intranasal administration for AD increased the overall brain accrual to 248.1% with a direct transport efficiency of 59.7% (Li et al, 2023).…”

“…(c) Transferrin-modified nano-polymer negatively used for nose-to-brain schematic diagram (Sonali, Singh, et al, 2016b). (d) Self-assembled curcumin-lactoferrin nanoparticles for the treatment of AD (Li et al, 2023).…”