<p>The Optimization Design Of Lactoferrin Loaded HupA Nanoemulsion For Targeted Drug Transport Via Intranasal Route</p>

Abstract

BackgroundHuperzine A (HupA) is a selective acetylcholinesterase inhibitor used to treat Alzheimer’s disease. The existing dosage of HupA lacks brain selectivity and can cause serious side effects in the gastrointestinal and peripheral cholinergic systems.PurposeThe aim of this study was to develop and characterize a HupA nanoemulsion (NE) and a targeted HupA-NE modified with lactoferrin (Lf) for intranasal administration.MethodsThe NE was formulated using pseudo-ternary phase diagrams and optimized with response surface methodology. Particle size distribution and zeta potential were evaluated, and transmission electron microscopy was performed. We investigated the transport mechanisms of HupA-NEs into hCMEC/D3 cells, an in vitro model of the blood-brain barrier. HupA-NE, Lf-HupA-NE, and HupA solution were intranasally administered to rats to investigate the brain-targeting effects of these formulations. A drug targeting index (DTI) was calculated to determine brain-targeting efficiency.ResultsOptimized HupA-NE had a particle size of 15.24±0.67 nm, polydispersity index (PDI) of 0.128±0.025, and zeta potential of −4.48±0.97 mV. The composition of the optimized HupA-NE was 3.00% isopropyl myristate (IPM), 3.81% Capryol 90, and 40% Cremophor EL + Labrasol. NEs, particularly Lf-HupA-NE, were taken up into hCMEC/D3 cells to a greater extent than pure drug alone. Western blot analysis showed that hCMEC/D3 cells contained P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance associated protein 1 (MRP1) transporters. The likely mechanisms resulting in higher NE transport to the brain were uptake by specific transporters and transcytosis. In vivo, intranasal Lf-HupA-NE significantly enhanced drug delivery to the brain compared to HupA-NE, which was confirmed by differences in pharmacokinetic parameters. The DTI of Lf-HupA-NE (3.2±0.75) demonstrated brain targeting, and the area under the curve for Lf-HupA-NE was significantly higher than that for HupA-NE.ConclusionLf-HupA-NE is a promising nasal drug delivery carrier for facilitating delivery of HupA to the central nervous system.

Nanotechnology-Based Drug Delivery Strategies to Repair the Mitochondrial Function in Neuroinflammatory and Neurodegenerative Diseases

“…Huperzine A (HupA) is an alkaloid from some plants of genus Huperzia used as therapy for memory deficits and acetylcholine-deficit dementia such as AD [246] and to repair mitochondrial function by preserving membrane structural integrity and activity of ETC complexes as well as ATP synthesis in cellular and animal models of AD [247,248]. Nanosystems containing HupA have been described showing enhanced drug delivery compared to free drug or non-targeted NF in mouse brain after intranasal administration [249,250]. In addtion, PEG-PLGA NPs containing HupA show a higher memory recovery than free HupA in AD rats [251].…”

Intranasal Nanoemulsions for Direct Nose-to-Brain Delivery of Actives for CNS Disorders

“…The intranasal administration of lactoferrin-HupA-NE in rats significantly ( p < 0.05) enhanced drug delivery to the brain compared to HupA-NE. The direct targeting index of lactoferrin-HupA-NE (3.21 ± 0.75) demonstrated brain targeting, and the area under the curve (AUC) 0–α for lactoferrin-HupA-NE was significantly higher ( p < 0.05) compared to HupA-NE [ 66 ].…”

Microbial acetylcholinesterase inhibitors for Alzheimer’s therapy: recent trends on extraction, detection, irradiation-assisted production improvement and nano-structured drug delivery

“…Oil-in-water nano-emulsions are cloudy and surfactantstabilized heterogeneous drug delivery systems; they are composed of oil droplets (10-100 nm) dispersed in water or other aqueous solutions (Hort et al 2019;Karami et al 2019). On the other hand, nano-emulsions can be effectively used to encapsulate HupA with high protection against degradation and can be produced at the large scale (Jiang et al 2019). Jiang et al (2019) reported a new nano-emulsion-based system loaded with Lactoferrin for enhanced targeted drug delivery via intranasal administration.…”

“…On the other hand, nano-emulsions can be effectively used to encapsulate HupA with high protection against degradation and can be produced at the large scale (Jiang et al 2019). Jiang et al (2019) reported a new nano-emulsion-based system loaded with Lactoferrin for enhanced targeted drug delivery via intranasal administration. Their results showed the successful targeting of hCMEC/D3 cells, and their system is non-toxic and was highly stable up to 6 months (Jiang et al 2019).…”

“…Jiang et al (2019) reported a new nano-emulsion-based system loaded with Lactoferrin for enhanced targeted drug delivery via intranasal administration. Their results showed the successful targeting of hCMEC/D3 cells, and their system is non-toxic and was highly stable up to 6 months (Jiang et al 2019).…”