Development and Evaluation of Solid Lipid Nanoparticles for the Clearance of Aβ in Alzheimer’s Disease

Shivananjegowda, Meghana Goravinahalli; Hani, Umme; Osmani, Riyaz Ali M.; Alamri, Ali H.; Ghazwani, Mohammed; Alhamhoom, Yahya; Rahamathulla, Mohamed; Paranthaman, Sathishbabu; Gowda, Devegowda Vishakante; Siddiqua, Ayesha

doi:10.3390/pharmaceutics15010221

Cited by 21 publications

(7 citation statements)

References 40 publications

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“…Similarly, NLCs are modified SLNs in which the lipid phase consists of liquid lipids (oils) and solids at room temperature . The small size and lipid nature of SLNs and NLCs facilitate crossing the BBB, especially in the leaky tumor vasculature. , Regarding drug delivery to the CNS, both SLNs and NLCs have been confirmed to improve the treatment of several neurological diseases, such as Parkinson’s disease, Alzheimer’s disease, migraine, epilepsy, and brain cancer . Many studies demonstrated the superiority of NLCs and SLNs over other nanoparticles (e.g., PLGA NPs) to promote targeted delivery of drugs to the brain due to their lipid properties. − …”

Section: Permeation Mechanisms Of Nanoparticles Capable Of Crossing T...mentioning

confidence: 99%

Functionalized Nanomaterials Capable of Crossing the Blood–Brain Barrier

Zha,

Liu,

et al. 2024

ACS Nano

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The blood−brain barrier (BBB) is a specialized semipermeable structure that highly regulates exchanges between the central nervous system parenchyma and blood vessels. Thus, the BBB also prevents the passage of various forms of therapeutic agents, nanocarriers, and their cargos. Recently, many multidisciplinary studies focus on developing cargo-loaded nanoparticles (NPs) to overcome these challenges, which are emerging as safe and effective vehicles in neurotheranostics. In this Review, first we introduce the anatomical structure and physiological functions of the BBB. Second, we present the endogenous and exogenous transport mechanisms by which NPs cross the BBB. We report various forms of nanomaterials, carriers, and their cargos, with their detailed BBB uptake and permeability characteristics. Third, we describe the effect of regulating the size, shape, charge, and surface ligands of NPs that affect their BBB permeability, which can be exploited to enhance and promote neurotheranostics. We classify typical functionalized nanomaterials developed for BBB crossing. Fourth, we provide a comprehensive review of the recent progress in developing functional polymeric nanomaterials for applications in multimodal bioimaging, therapeutics, and drug delivery. Finally, we conclude by discussing existing challenges, directions, and future perspectives in employing functionalized nanomaterials for BBB crossing.

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Section: Permeation Mechanisms Of Nanoparticles Capable Of Crossing T...mentioning

confidence: 99%

Functionalized Nanomaterials Capable of Crossing the Blood–Brain Barrier

Zha,

Liu,

et al. 2024

ACS Nano

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“…However, the specific neuroprotective mechanisms remain unclear. In this approach, Shivananjegowda et al [ 13 ] found that SLNps formulated using memantine hydrochloride (MeHCl) and tramiprosate (TMPS) confirmed the metabolic degradation of A β on SH-SY5Y cells.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effect of Solid Lipid Nanoparticles Loaded with Lepidium sativum (L.) Seed Bioactive Components Enhance Bioavailability and Wnt/β-Catenin/Camk-II Signaling Cascade in SH-SY5Y Neuroblastoma Cells

Al-Saran,

Subash-Babu,

Al-Harbi

et al. 2024

Nanomaterials

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The primary pathological hallmark of Alzheimer’s disease (AD) is the formation and accumulation of neurofibrillary tangles and plaques, which result from the aggregation of amyloid-β (Aβ) induced by oxidative stress. The effectiveness of Alzheimer’s disease (AD) therapeutics significantly hinges on the drug’s bioavailability and its ability to penetrate neuronal cells. The current investigation was designed as a first attempt to examine bio-fabricated Lepidium sativum (LS) seed-extract-loaded solid lipid nanoparticles (SLNps) to increase bioavailability and bioefficacy for the prevention of undifferentiated SH-SY5Y neuronal cells from oxidative stress induced by H2O2 and amyloid-β peptide (Aβ,1-42). The SLNps were fabricated using LS extract as a water phase and hyaluronic acid and chia seed fatty acids as a lipid phase, then confirmed and characterized using UV, Zeta size, and SEM methods. The biological safety of synthesized LS-SLNps has been determined using MTT assay and PI staining (nuclear damage) in hMSCs. LS-SLNp-pretreated neuronal cells were induced with oxidative stress and 2 µM of beta-amyloid (Aβ,1-42) fibrils; furthermore, the neuroprotective potential of LS-SLNps was determined through the quenching of oxidative stress, enhancing mitochondrial oxidative capacity, and immunoregulatory potential. Observations found that cells treated with both H2O2 and beta-amyloid (Aβ,1-42) fibrils showed decreased neuronal cell growth, nuclear damage, and mitochondrial membrane potential due to oxidative stress. However, SH-SY5Y cells pretreated with LS-SLNps for 24 h showed an increase in cell proliferation with uniform morphology and increased mitochondrial membrane potential compared to cells pretreated with LS alone. Gene expression analysis found that LS-SLNps increased the expression of Wnt 3a and 5a, which stimulated the canonical, β-catenin, and non-canonical Camk-II expressions of nerve cell growth factors, confirming the molecular-level reversal of neurodegenerative diseases.

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“…A tricyclic antidepressant (TCI) is also used for neuroleptic pain . AMX is also used to reduce antibiotic resistance and inhibit mycobacterial infections . AMX is an N-desmethyl derivative of loxapine with noradrenaline reuptake inhibition, 5-HT receptor antagonism, and dopamine D2 receptor antagonism .…”

Section: Introductionmentioning

confidence: 99%

“…SLNs and other nanoparticle formulations can increase drug bioavailability. In recent studies, memantine hydrochloride (MeHCl) and tramiprosate (TMPS)-loaded solid lipid nanoparticles were prepared to treat Alzheimer’s disease . SLN is a suitable delivery system for poorly aqueous-soluble drugs due to its biocompatible lipids and ability to entrap lipophilic molecules.…”

Section: Introductionmentioning

confidence: 99%

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Amoxapine-Loaded Solid Lipid Nanoparticles with Superior Preclinical Pharmacokinetics for Better Brain Delivery: LC-MS/MS and GC-MS Analysis

Pawar

Gawali

Kulhari

et al. 2023

ACS Chem. Neurosci.

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The tricyclic antidepressant amoxapine (AMX) has been reported for a rapid onset of action compared to other cyclic antidepressants. It has very low solubility and bioavailability due to first-pass metabolism. Therefore, we planned to develop solid lipid nanoparticles (SLNs) of AMX using a single emulsification method to increase its solubility and bioavailability. HPLC and LC-MS/MS methods were developed further to quantify AMX in the formulation, plasma, and brain tissue samples. The formulation was studied for entrapment efficiency, loading, and in vitro drug release. Particle size and ζ potential analyses, AFM, SEM, TEM, DSC, and XRD were used for further characterization. In vivo oral pharmacokinetic and brain pharmacokinetic studies were performed using Wistar rats. The entrapment and loading efficiencies of AMX in SLNs were 85.8 ± 3.42 and 4.5 ± 0.45%, respectively. The developed formulation had a mean particle size of 151.5 ± 7.02 nm and a polydispersity index of 0.40 ± 0.11. DSC and XRD results indicated that AMX was incorporated into the nanocarrier system in an amorphous form. SEM, TEM, and AFM studies of AMX-SLNs confirmed the particles’ spherical shape and nanoscale size. AMX solubility increased by approx. 2.67 times compared to the pure drug. The developed LC-MS/MS method was successfully applied to the oral and brain pharmacokinetic study of AMX-loaded SLNs in rats. Oral bioavailability was enhanced 1.6 times compared to the pure drug. The peak plasma concentrations of pure AMX and AMX-SLNs were 617.4 ± 137.4 and 1043.5 ± 150.2 (ng/mL), respectively. AMX-SLNs showed more than 5.8 times brain concentration compared to the pure drug. Based on the findings, it appears that utilizing a solid lipid nanoparticle carrier to transport AMX can be a highly effective delivery method with improved pharmacokinetic properties in the brain. This approach may prove valuable for future antidepressant treatment.

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Development and Evaluation of Solid Lipid Nanoparticles for the Clearance of Aβ in Alzheimer’s Disease

Cited by 21 publications

References 40 publications

Functionalized Nanomaterials Capable of Crossing the Blood–Brain Barrier

Functionalized Nanomaterials Capable of Crossing the Blood–Brain Barrier

Neuroprotective Effect of Solid Lipid Nanoparticles Loaded with Lepidium sativum (L.) Seed Bioactive Components Enhance Bioavailability and Wnt/β-Catenin/Camk-II Signaling Cascade in SH-SY5Y Neuroblastoma Cells

Amoxapine-Loaded Solid Lipid Nanoparticles with Superior Preclinical Pharmacokinetics for Better Brain Delivery: LC-MS/MS and GC-MS Analysis

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